Redox Signaling from Mitochondria: Signal Propagation and Its Targets

. 2020 Jan 06 ; 10 (1) : . [epub] 20200106

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid31935965

Grantová podpora
17-01813S Grantová Agentura České Republiky - International

Progress in mass spectroscopy of posttranslational oxidative modifications has enabled researchers to experimentally verify the concept of redox signaling. We focus here on redox signaling originating from mitochondria under physiological situations, discussing mechanisms of transient redox burst in mitochondria, as well as the possible ways to transfer such redox signals to specific extramitochondrial targets. A role of peroxiredoxins is described which enables redox relay to other targets. Examples of mitochondrial redox signaling are discussed: initiation of hypoxia-inducible factor (HIF) responses; retrograde redox signaling to PGC1α during exercise in skeletal muscle; redox signaling in innate immune cells; redox stimulation of insulin secretion, and other physiological situations.

Zobrazit více v PubMed

Parvez S., Long M.J.C., Poganik J.R., Aye Y. Redox Signaling by Reactive Electrophiles and Oxidants. Chem. Rev. 2018;118:8798–8888. doi: 10.1021/acs.chemrev.7b00698. PubMed DOI PMC

Reczek C.R., Chandel N.S. ROS-dependent signal transduction. Curr. Opin. Cell Biol. 2015;33:8–13. doi: 10.1016/j.ceb.2014.09.010. PubMed DOI PMC

Skoko J.J., Attaran S., Neumann C.A. Signals Getting Crossed in the Entanglement of Redox and Phosphorylation Pathways: Phosphorylation of Peroxiredoxin Proteins Sparks Cell Signaling. Antioxid. Basel. 2019;8:29. doi: 10.3390/antiox8020029. PubMed DOI PMC

Shadel G.S., Horvath T.L. Mitochondrial ROS signaling in organismal homeostasis. Cell. 2015;163:560–569. doi: 10.1016/j.cell.2015.10.001. PubMed DOI PMC

Plecita-Hlavata L., Tauber J., Li M., Zhang H., Flockton A.R., Pullamsetti S.S., Chelladurai P., D’Alessandro A., El Kasmi K.C., Jezek P., et al. Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension. Am. J. Respir. Cell Mol. Biol. 2016;55:47–57. doi: 10.1165/rcmb.2015-0142OC. PubMed DOI PMC

D’Alessandro A., El Kasmi K.C., Plecitá-Hlavatá L., Ježek P., Li M., Zhang H., Gupte S.A., Stenmark K.R. Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming. Antioxid. Redox Signal. 2018;28:230–250. doi: 10.1089/ars.2017.7217. PubMed DOI PMC

Collins Y., Chouchani E.T., James A.M., Menger K.E., Cocheme H.M., Murphy M.P. Mitochondrial redox signalling at a glance. J. Cell Sci. 2012;125:801–806. doi: 10.1242/jcs.098475. PubMed DOI

Diebold L., Chandel N.S. Mitochondrial ROS regulation of proliferating cells. Free Radic. Biol. Med. 2016;100:86–93. doi: 10.1016/j.freeradbiomed.2016.04.198. PubMed DOI

Indo H.P., Hawkins C.L., Nakanishi I., Matsumoto K.I., Matsui H., Suenaga S., Davies M.J., St Clair D.K., Ozawa T., Majima H.J. Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function. In: Singh H., Sheu S.S., editors. Pharmacology of Mitochondria. Volume 240. Springer; Basel, Switzerland: 2017. pp. 439–456. PubMed DOI

Brand M.D. Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic. Biol. Med. 2016;100:14–31. doi: 10.1016/j.freeradbiomed.2016.04.001. PubMed DOI

Quinlan C.L., Perevoshchikova I.V., Hey-Mogensen M., Orr A.L., Brand M.D. Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biol. 2013;1:304–312. doi: 10.1016/j.redox.2013.04.005. PubMed DOI PMC

Ježek P., Hlavatá L. Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int. J. Biochem. Cell Biol. 2005;37:2478–2503. doi: 10.1016/j.biocel.2005.05.013. PubMed DOI

Plecitá-Hlavatá L., Ježek P. Integration of superoxide formation and cristae morphology for mitochondrial redox signaling. Int. J. Biochem. Cell Biol. 2016;80:31–50. doi: 10.1016/j.biocel.2016.09.010. PubMed DOI

Ježek P., Jabůrek M., Porter R.K. Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1) Biochim. Biophys. Acta BBA Bioenerg. 2019;1860:259–269. doi: 10.1016/j.bbabio.2018.11.007. PubMed DOI

Jezek P., Holendova B., Garlid K.D., Jaburek M. Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling. Antioxid. Redox Signal. 2018;29:667–714. doi: 10.1089/ars.2017.7225. PubMed DOI PMC

Ježek J., Engstová H., Ježek P. Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation. Biochim. Biophys. Acta Bioenerg. 2017;1858:750–762. doi: 10.1016/j.bbabio.2017.05.005. PubMed DOI

Pryde K.R., Hirst J. Superoxide is produced by the reduced flavin in mitochondrial complex I: A single, unified mechanism that applies during both forward and reverse electron transfer. J. Biol. Chem. 2011;286:18056–18065. doi: 10.1074/jbc.M110.186841. PubMed DOI PMC

Treberg J.R., Quinlan C.L., Brand M.D. Evidence for Two Sites of Superoxide Production by Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex I) J. Biol. Chem. 2011;286:27103–27110. doi: 10.1074/jbc.M111.252502. PubMed DOI PMC

Fuhrmann D.C., Brune B. Mitochondrial composition and function under the control of hypoxia. Redox Biol. 2017;12:208–215. doi: 10.1016/j.redox.2017.02.012. PubMed DOI PMC

Zepeda A.B., Pessoa A., Jr., Castillo R.L., Figueroa C.A., Pulgar V.M., Farias J.G. Cellular and molecular mechanisms in the hypoxic tissue: Role of HIF-1 and ROS. Cell Biochem. Funct. 2013;31:451–459. doi: 10.1002/cbf.2985. PubMed DOI

Semenza G.L. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148:399–408. doi: 10.1016/j.cell.2012.01.021. PubMed DOI PMC

Brunelle J.K., Bell E.L., Quesada N.M., Vercauteren K., Tiranti V., Zeviani M., Scarpulla R.C., Chandel N.S. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab. 2005;1:409–414. doi: 10.1016/j.cmet.2005.05.002. PubMed DOI

Smolková K., Plecitá-Hlavatá L., Bellance N., Benard G., Rossignol R., Ježek P. Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells. Int. J. Biochem. Cell Biol. 2011;43:950–968. doi: 10.1016/j.biocel.2010.05.003. PubMed DOI

DeBerardinis R.J., Chandel N.S. Fundamentals of cancer metabolism. Sci. Adv. 2016;2:e1600200. doi: 10.1126/sciadv.1600200. PubMed DOI PMC

Jezek P. 2-hydroxyglutarate in cancer cells. Antioxid. Redox Signal. 2019 doi: 10.1089/ars.2019.7902. PubMed DOI PMC

Dikalov S.I., Nazarewicz R.R., Bikineyeva A., Hilenski L., Lassegue B., Griendling K.K., Harrison D.G., Dikalova A.E. Nox2-induced production of mitochondrial superoxide in angiotensin II-mediated endothelial oxidative stress and hypertension. Antioxid. Redox Signal. 2014;20:281–294. doi: 10.1089/ars.2012.4918. PubMed DOI PMC

Plecitá-Hlavatá L., D’alessandro A., El Kasmi K., Li M., Zhang H., Ježek P., Stenmark K.R. Pulmonary Vasculature Redox Signaling in Health and Disease. Springer; Berlin, Germany: 2017. Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension; pp. 241–260. PubMed DOI

Ježek P., Holendová B., Jabůrek M., Tauber J., Plecitá-Hlavatá L. Mitochondrial Redox Signaling Upon 2-keto-isocaproate Stimulated Insulin Secretion. Free Radic. Biol. Med. 2019;145:S88.

Ježek P., Jabůrek M., Plecitá-Hlavatá L. Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes. Antioxid. Redox Signal. 2019;31:722–751. doi: 10.1089/ars.2018.7656. PubMed DOI PMC

Hood D.A., Memme J.M., Oliveira A.N., Triolo M. Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging. Annu. Rev. Physiol. 2019;81:19–41. doi: 10.1146/annurev-physiol-020518-114310. PubMed DOI

Horn A., Van der Meulen J.H., Defour A., Hogarth M., Sreetama S.C., Reed A., Scheffer L., Chandel N.S., Jaiswal J.K. Mitochondrial redox signaling enables repair of injured skeletal muscle cells. Sci. Signal. 2017;10 doi: 10.1126/scisignal.aaj1978. PubMed DOI PMC

Carter H.N., Pauly M., Tryon L.D., Hood D.A. Effect of contractile activity on PGC-1alpha transcription in young and aged skeletal muscle. J. Appl. Physiol. 2018;124:1605–1615. doi: 10.1152/japplphysiol.01110.2017. PubMed DOI

Garcia S., Nissanka N., Mareco E.A., Rossi S., Peralta S., Diaz F., Rotundo R.L., Carvalho R.F., Moraes C.T. Overexpression of PGC-1alpha in aging muscle enhances a subset of young-like molecular patterns. Aging Cell. 2018;17 doi: 10.1111/acel.12707. PubMed DOI PMC

Halling J.F., Ringholm S., Olesen J., Prats C., Pilegaard H. Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1alpha dependent manner. Exp. Gerontol. 2017;96:1–6. doi: 10.1016/j.exger.2017.05.020. PubMed DOI

Chouchani E.T., Pell V.R., Gaude E., Aksentijević D., Sundier S.Y., Robb E.L., Logan A., Nadtochiy S.M., Ord E.N.J., Smith A.C., et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–435. doi: 10.1038/nature13909. PubMed DOI PMC

Chouchani E.T., Kazak L., Jedrychowski M.P., Lu G.Z., Erickson B.K., Szpyt J., Pierce K.A., Laznik-Bogoslavski D., Vetrivelan R., Clish C.B., et al. Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. Nature. 2016;532:112–116. doi: 10.1038/nature17399. PubMed DOI PMC

Sena L.A., Li S., Jairaman A., Prakriya M., Ezponda T., Hildeman D.A., Wang C.R., Schumacker P.T., Licht J.D., Perlman H., et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38:225–236. doi: 10.1016/j.immuni.2012.10.020. PubMed DOI PMC

Kaminski M.M., Sauer S.W., Klemke C.D., Suss D., Okun J.G., Krammer P.H., Gulow K. Mitochondrial reactive oxygen species control T cell activation by regulating IL-2 and IL-4 expression: Mechanism of ciprofloxacin-mediated immunosuppression. J. Immunol. 2010;184:4827–4841. doi: 10.4049/jimmunol.0901662. PubMed DOI

Zhou R., Yazdi A.S., Menu P., Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221–225. doi: 10.1038/nature09663. PubMed DOI

Bleier L., Dröse S. Superoxide generation by complex III: From mechanistic rationales to functional consequences. Biochim. Biophys. Acta BBA Bioenergy. 2013;1827:1320–1331. doi: 10.1016/j.bbabio.2012.12.002. PubMed DOI

Dröse S., Brandt U. Advances in Experimental Medicine and Biology. Volume 748. Springer; Berlin, Germany: 2012. Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain; pp. 145–169. PubMed

Chouchani E.T., Methner C., Buonincontri G., Hu C.H., Logan A., Sawiak S.J., Murphy M.P., Krieg T. Complex I deficiency due to selective loss of Ndufs4 in the mouse heart results in severe hypertrophic cardiomyopathy. PLoS ONE. 2014;9:e94157. doi: 10.1371/journal.pone.0094157. PubMed DOI PMC

Chouchani E.T., Kazak L., Spiegelman B.M. Mitochondrial reactive oxygen species and adipose tissue thermogenesis: Bridging physiology and mechanisms. J. Biol. Chem. 2017;292:16810–16816. doi: 10.1074/jbc.R117.789628. PubMed DOI PMC

Mills E.L., Pierce K.A., Jedrychowski M.P., Garrity R., Winther S., Vidoni S., Yoneshiro T., Spinelli J.B., Lu G.Z., Kazak L., et al. Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature. 2018;560:102–106. doi: 10.1038/s41586-018-0353-2. PubMed DOI PMC

Ježek J., Dlasková A., Zelenka J., Jabůrek M., Ježek P. H2O2-Activated Mitochondrial Phospholipase iPLA2γ Prevents Lipotoxic Oxidative Stress in Synergy with UCP2, Amplifies Signaling via G-Protein–Coupled Receptor GPR40, and Regulates Insulin Secretion in Pancreatic β-Cells. Antioxid. Redox Signal. 2015;23:958–972. doi: 10.1089/ars.2014.6195. PubMed DOI PMC

O-Uhi J., Ryu S.Y., Jhun B.S., Hurst S., Sheu S.S. Mitochondrial ion channels/transporters as sensors and regulators of cellular redox signaling. Antioxid. Redox Signal. 2014;21:987–1006. doi: 10.1089/ars.2013.5681. PubMed DOI PMC

Borecky J., Jezek P., Siemen D. 108-pS channel in brown fat mitochondria might Be identical to the inner membrane anion channel. J. Biol. Chem. 1997;272:19282–19289. PubMed

Jezek P., Borecky J. Inner membrane anion channel and dicarboxylate carrier in brown adipose tissue mitochondria. Int. J. Biochem. Cell Biol. 1996;28:659–666. doi: 10.1016/1357-2725(96)00008-8. PubMed DOI

Zorov D.B., Juhaszova M., Sollott S.J. Mitochondrial ROS-induced ROS release: An update and review. Biochim. Biophys. Acta. 2006;1757:509–517. doi: 10.1016/j.bbabio.2006.04.029. PubMed DOI

Brady N.R., Hamacher-Brady A., Westerhoff H.V., Gottlieb R.A. A wave of reactive oxygen species (ROS)-induced ROS release in a sea of excitable mitochondria. Antioxid. Redox Signal. 2006;8:1651–1665. doi: 10.1089/ars.2006.8.1651. PubMed DOI

Aon M.A., Cortassa S., Marban E., O’Rourke B. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J. Biol. Chem. 2003;278:44735–44744. doi: 10.1074/jbc.M302673200. PubMed DOI

Aon M.A., Cortassa S., O’Rourke B. Redox-optimized ROS balance: A unifying hypothesis. Biochim. Biophys. Acta. 2010;1797:865–877. doi: 10.1016/j.bbabio.2010.02.016. PubMed DOI PMC

Urbani A., Giorgio V., Carrer A., Franchin C., Arrigoni G., Jiko C., Abe K., Maeda S., Shinzawa-Itoh K., Bogers J.F.M., et al. Purified F-ATP synthase forms a Ca(2+)-dependent high-conductance channel matching the mitochondrial permeability transition pore. Nat. Commun. 2019;10:4341. doi: 10.1038/s41467-019-12331-1. PubMed DOI PMC

Chen Y., Azad M.B., Gibson S.B. Superoxide is the major reactive oxygen species regulating autophagy. Cell Death Differ. 2009;16:1040–1052. doi: 10.1038/cdd.2009.49. PubMed DOI

Buntinas L., Gunter K.K., Sparagna G.C., Gunter T.E. The rapid mode of calcium uptake into heart mitochondria (RaM): Comparison to RaM in liver mitochondria. Biochim. Biophys. Acta. 2001;1504:248–261. doi: 10.1016/S0005-2728(00)00254-1. PubMed DOI

Sparagna G.C., Gunter K.K., Sheu S.S., Gunter T.E. Mitochondrial calcium uptake from physiological-type pulses of calcium. A description of the rapid uptake mode. J. Biol. Chem. 1995;270:27510–27515. doi: 10.1074/jbc.270.46.27510. PubMed DOI

Jiang D., Zhao L., Clapham D.E. Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Sci. N. Y. 2009;326:144–147. doi: 10.1126/science.1175145. PubMed DOI PMC

Bogeski I., Gulaboski R., Kappl R., Mirceski V., Stefova M., Petreska J., Hoth M. Calcium binding and transport by coenzyme Q. J. Am. Chem. Soc. 2011;133:9293–9303. doi: 10.1021/ja110190t. PubMed DOI

Beutner G., Sharma V.K., Giovannucci D.R., Yule D.I., Sheu S.S. Identification of a ryanodine receptor in rat heart mitochondria. J. Biol. Chem. 2001;276:21482–21488. doi: 10.1074/jbc.M101486200. PubMed DOI

Beutner G., Sharma V.K., Lin L., Ryu S.Y., Dirksen R.T., Sheu S.S. Type 1 ryanodine receptor in cardiac mitochondria: Transducer of excitation-metabolism coupling. Biochim. Biophys. Acta. 2005;1717:1–10. doi: 10.1016/j.bbamem.2005.09.016. PubMed DOI

Ryu S.Y., Beutner G., Kinnally K.W., Dirksen R.T., Sheu S.S. Single channel characterization of the mitochondrial ryanodine receptor in heart mitoplasts. J. Biol. Chem. 2011;286:21324–21329. doi: 10.1074/jbc.C111.245597. PubMed DOI PMC

Chaudhuri D., Sancak Y., Mootha V.K., Clapham D.E. MCU encodes the pore conducting mitochondrial calcium currents. eLife. 2013;2:e00704. doi: 10.7554/eLife.00704. PubMed DOI PMC

Kirichok Y., Krapivinsky G., Clapham D.E. The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 2004;427:360–364. doi: 10.1038/nature02246. PubMed DOI

Mammucari C., Raffaello A., Vecellio Reane D., Gherardi G., De Mario A., Rizzuto R. Mitochondrial calcium uptake in organ physiology: From molecular mechanism to animal models. Pflug. Arch. Eur. J. Physiol. 2018;470:1165–1179. doi: 10.1007/s00424-018-2123-2. PubMed DOI PMC

Dong Z., Shanmughapriya S., Tomar D., Siddiqui N., Lynch S., Nemani N., Breves S.L., Zhang X., Tripathi A., Palaniappan P., et al. Mitochondrial Ca(2+) Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity. Mol. Cell. 2017;65:1014–1028.e1017. doi: 10.1016/j.molcel.2017.01.032. PubMed DOI PMC

Laskowski M., Augustynek B., Kulawiak B., Koprowski P., Bednarczyk P., Jarmuszkiewicz W., Szewczyk A. What do we not know about mitochondrial potassium channels? Biochim. Biophys. Acta. 2016;1857:1247–1257. doi: 10.1016/j.bbabio.2016.03.007. PubMed DOI

Checchetto V., Azzolini M., Peruzzo R., Capitanio P., Leanza L. Mitochondrial potassium channels in cell death. Biochem. Biophys. Res. Commun. 2018;500:51–58. doi: 10.1016/j.bbrc.2017.06.095. PubMed DOI

Bernardi P. Mitochondrial transport of cations: Channels, exchangers, and permeability transition. Physiol. Rev. 1999;79:1127–1155. doi: 10.1152/physrev.1999.79.4.1127. PubMed DOI

Li X.Q., Hegazy M.G., Mahdi F., Jezek P., Lane R.D., Garlid K.D. Purification of a reconstitutively active K+/H+ antiporter from rat liver mitochondria. J. Biol. Chem. 1990;265:15316–15322. PubMed

Jezek P., Mahdi F., Garlid K.D. Reconstitution of the beef heart and rat liver mitochondrial K+/H+ (Na+/H+) antiporter. Quantitation of K+ transport with the novel fluorescent probe, PBFI. J. Biol. Chem. 1990;265:10522–10526. PubMed

Zotova L., Aleschko M., Sponder G., Baumgartner R., Reipert S., Prinz M., Schweyen R.J., Nowikovsky K. Novel components of an active mitochondrial K(+)/H(+) exchange. J. Biol. Chem. 2010;285:14399–14414. doi: 10.1074/jbc.M109.059956. PubMed DOI PMC

Nazarewicz R.R., Dikalova A.E., Bikineyeva A., Dikalov S.I. Nox2 as a potential target of mitochondrial superoxide and its role in endothelial oxidative stress. Am. J. Physiol. Heart Circ. Physiol. 2013;305:H1131–H1140. doi: 10.1152/ajpheart.00063.2013. PubMed DOI PMC

Queliconi B.B., Wojtovich A.P., Nadtochiy S.M., Kowaltowski A.J., Brookes P.S. Redox regulation of the mitochondrial K(ATP) channel in cardioprotection. Biochim. Biophys. Acta. 2011;1813:1309–1315. doi: 10.1016/j.bbamcr.2010.11.005. PubMed DOI PMC

Shoshan-Barmatz V., Zakar M., Rosenthal K., Abu-Hamad S. Key regions of VDAC1 functioning in apoptosis induction and regulation by hexokinase. Biochim. Biophys. Acta. 2009;1787:421–430. doi: 10.1016/j.bbabio.2008.11.009. PubMed DOI

Maldonado E.N., Sheldon K.L., DeHart D.N., Patnaik J., Manevich Y., Townsend D.M., Bezrukov S.M., Rostovtseva T.K., Lemasters J.J. Voltage-dependent anion channels modulate mitochondrial metabolism in cancer cells: Regulation by free tubulin and erastin. J. Biol. Chem. 2013;288:11920–11929. doi: 10.1074/jbc.M112.433847. PubMed DOI PMC

Sheldon K.L., Gurnev P.A., Bezrukov S.M., Sackett D.L. Tubulin tail sequences and post-translational modifications regulate closure of mitochondrial voltage-dependent anion channel (VDAC) J. Biol. Chem. 2015;290:26784–26789. doi: 10.1074/jbc.M115.678854. PubMed DOI PMC

Schwarzer C., Barnikol-Watanabe S., Thinnes F.P., Hilschmann N. Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74. Int. J. Biochem. Cell Biol. 2002;34:1059–1070. doi: 10.1016/S1357-2725(02)00026-2. PubMed DOI

Xu X., Forbes J.G., Colombini M. Actin modulates the gating of Neurospora crassa VDAC. J. Membr. Biol. 2001;180:73–81. doi: 10.1007/s002320010060. PubMed DOI

Saletti R., Reina S., Pittala M.G.G., Magri A., Cunsolo V., Foti S., De Pinto V. Post-translational modifications of VDAC1 and VDAC2 cysteines from rat liver mitochondria. Biochim. Biophys. Acta. Bioenerg. 2018;1859:806–816. doi: 10.1016/j.bbabio.2018.06.007. PubMed DOI

Shimizu S., Narita M., Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 1999;399:483–487. doi: 10.1038/20959. PubMed DOI

Cheng E.H., Sheiko T.V., Fisher J.K., Craigen W.J., Korsmeyer S.J. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Sci. N. Y. 2003;301:513–517. doi: 10.1126/science.1083995. PubMed DOI

Reina S., Checchetto V., Saletti R., Gupta A., Chaturvedi D., Guardiani C., Guarino F., Scorciapino M.A., Magri A., Foti S., et al. VDAC3 as a sensor of oxidative state of the intermembrane space of mitochondria: The putative role of cysteine residue modifications. Oncotarget. 2016;7:2249–2268. doi: 10.18632/oncotarget.6850. PubMed DOI PMC

Martel C., Wang Z., Brenner C. VDAC phosphorylation, a lipid sensor influencing the cell fate. Mitochondrion. 2014;19:69–77. doi: 10.1016/j.mito.2014.07.009. PubMed DOI

Yu H., Diao H., Wang C., Lin Y., Yu F., Lu H., Xu W., Li Z., Shi H., Zhao S., et al. Acetylproteomic analysis reveals functional implications of lysine acetylation in human spermatozoa (sperm) Mol. Cell. Proteom. MCP. 2015;14:1009–1023. doi: 10.1074/mcp.M114.041384. PubMed DOI PMC

Yang M., Camara A.K., Wakim B.T., Zhou Y., Gadicherla A.K., Kwok W.M., Stowe D.F. Tyrosine nitration of voltage-dependent anion channels in cardiac ischemia-reperfusion: Reduction by peroxynitrite scavenging. Biochim. Biophys. Acta. 2012;1817:2049–2059. doi: 10.1016/j.bbabio.2012.06.004. PubMed DOI PMC

Fu L., Liu K., Ferreira R.B., Carroll K.S., Yang J. Proteome-Wide Analysis of Cysteine S-Sulfenylation Using a Benzothiazine-Based Probe. Curr. Protoc. Protein Sci. 2019;95:e76. doi: 10.1002/cpps.76. PubMed DOI PMC

Van der Reest J., Lilla S., Zheng L., Zanivan S., Gottlieb E. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat. Commun. 2018;9:1581. doi: 10.1038/s41467-018-04003-3. PubMed DOI PMC

Boronat S., Domènech A., Hidalgo E. Proteomic Characterization of Reversible Thiol Oxidations in Proteomes and Proteins. Antioxid. Redox Signal. 2017;26:329–344. doi: 10.1089/ars.2016.6720. PubMed DOI

Bak D.W., Weerapana E. Interrogation of Functional Mitochondrial Cysteine Residues by Quantitative Mass Spectrometry. Methods Mol. Biol. Clifton. 2019;1967:211–227. doi: 10.1007/978-1-4939-9187-7_13. PubMed DOI PMC

Gould N.S. Site-Specific Proteomic Mapping of Modified Cysteine Residues. Methods Mol. Biol. Clifton. 2019;1967:183–195. doi: 10.1007/978-1-4939-9187-7_11. PubMed DOI

Abreu I.A., Cabelli D.E. Superoxide dismutases-a review of the metal-associated mechanistic variations. Biochim. Biophys. Acta. 2010;1804:263–274. doi: 10.1016/j.bbapap.2009.11.005. PubMed DOI

Bielski B.H.J., Allen A.O. Mechanism of the disproportionation of superoxide radicals. J. Phys. Chem. 1977;81:1048–1050. doi: 10.1021/j100526a005. DOI

Jones C.M., Lawrence A., Wardman P., Burkitt M.J. Kinetics of superoxide scavenging by glutathione: An evaluation of its role in the removal of mitochondrial superoxide. Biochem. Soc. Trans. 2003;31:1337–1339. doi: 10.1042/bst0311337. PubMed DOI

Mikkelsen R.B., Wardman P. Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms. Oncogene. 2003;22:5734–5754. doi: 10.1038/sj.onc.1206663. PubMed DOI

Venditti P., Di Stefano L., Di Meo S. Mitochondrial metabolism of reactive oxygen species. Mitochondrion. 2013;13:71–82. doi: 10.1016/j.mito.2013.01.008. PubMed DOI

Mishina N.M., Bogdanova Y.A., Ermakova Y.G., Panova A.S., Kotova D.A., Bilan D.S., Steinhorn B., Arner E.S.J., Michel T., Belousov V.V. Which Antioxidant System Shapes Intracellular H2O2 Gradients? Antioxid. Redox Signal. 2019;31:664–670. doi: 10.1089/ars.2018.7697. PubMed DOI PMC

Giorgio M., Trinei M., Migliaccio E., Pelicci P.G. Hydrogen peroxide: A metabolic by-product or a common mediator of ageing signals? Nat. Rev. Mol. Cell Biol. 2007;8:722–728. doi: 10.1038/nrm2240. PubMed DOI

Peskin A.V., Low F.M., Paton L.N., Maghzal G.J., Hampton M.B., Winterbourn C.C. The high reactivity of peroxiredoxin 2 with H(2)O(2) is not reflected in its reaction with other oxidants and thiol reagents. J. Biol. Chem. 2007;282:11885–11892. doi: 10.1074/jbc.M700339200. PubMed DOI

Lennicke C., Rahn J., Lichtenfels R., Wessjohann L.A., Seliger B. Hydrogen peroxide—Production, fate and role in redox signaling of tumor cells. Cell Commun. Signal. CCS. 2015;13:39. doi: 10.1186/s12964-015-0118-6. PubMed DOI PMC

Paulsen C.E., Carroll K.S. Cysteine-mediated redox signaling: Chemistry, biology, and tools for discovery. Chem. Rev. 2013;113:4633–4679. doi: 10.1021/cr300163e. PubMed DOI PMC

Poole L.B. The basics of thiols and cysteines in redox biology and chemistry. Free Radic. Biol. Med. 2015;80:148–157. doi: 10.1016/j.freeradbiomed.2014.11.013. PubMed DOI PMC

Hohn A., Jung T., Grune T. Pathophysiological importance of aggregated damaged proteins. Free Radic. Biol. Med. 2014;71:70–89. doi: 10.1016/j.freeradbiomed.2014.02.028. PubMed DOI

Rhee S.G. Overview on Peroxiredoxin. Mol. Cells. 2016;39:1–5. doi: 10.14348/molcells.2016.2368. PubMed DOI PMC

Wood Z.A., Poole L.B., Karplus P.A. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Sci. N. Y. 2003;300:650–653. doi: 10.1126/science.1080405. PubMed DOI

Kang S.W., Chae H.Z., Seo M.S., Kim K., Baines I.C., Rhee S.G. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J. Biol. Chem. 1998;273:6297–6302. doi: 10.1074/jbc.273.11.6297. PubMed DOI

Lim J.C., Choi H.I., Park Y.S., Nam H.W., Woo H.A., Kwon K.S., Kim Y.S., Rhee S.G., Kim K., Chae H.Z. Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity. J. Biol. Chem. 2008;283:28873–28880. doi: 10.1074/jbc.M804087200. PubMed DOI PMC

Knoops B., Goemaere J., Van der Eecken V., Declercq J.P. Peroxiredoxin 5: Structure, mechanism, and function of the mammalian atypical 2-Cys peroxiredoxin. Antioxid. Redox Signal. 2011;15:817–829. doi: 10.1089/ars.2010.3584. PubMed DOI

Rhee S.G., Kang S.W., Chang T.S., Jeong W., Kim K. Peroxiredoxin, a novel family of peroxidases. IUBMB Life. 2001;52:35–41. doi: 10.1080/15216540252774748. PubMed DOI

Fisher A.B. Peroxiredoxin 6: A bifunctional enzyme with glutathione peroxidase and phospholipase A(2) activities. Antioxid. Redox Signal. 2011;15:831–844. doi: 10.1089/ars.2010.3412. PubMed DOI PMC

Hall A., Parsonage D., Poole L.B., Karplus P.A. Structural evidence that peroxiredoxin catalytic power is based on transition-state stabilization. J. Mol. Biol. 2010;402:194–209. doi: 10.1016/j.jmb.2010.07.022. PubMed DOI PMC

Winterbourn C.C., Peskin A.V. Kinetic Approaches to Measuring Peroxiredoxin Reactivity. Mol. Cells. 2016;39:26–30. doi: 10.14348/molcells.2016.2325. PubMed DOI PMC

Marinho H.S., Real C., Cyrne L., Soares H., Antunes F. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol. 2014;2:535–562. doi: 10.1016/j.redox.2014.02.006. PubMed DOI PMC

Woo H.A., Yim S.H., Shin D.H., Kang D., Yu D.Y., Rhee S.G. Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. Cell. 2010;140:517–528. doi: 10.1016/j.cell.2010.01.009. PubMed DOI

Mishra M., Jiang H., Wu L., Chawsheen H.A., Wei Q. The sulfiredoxin-peroxiredoxin (Srx-Prx) axis in cell signal transduction and cancer development. Cancer Lett. 2015;366:150–159. doi: 10.1016/j.canlet.2015.07.002. PubMed DOI PMC

Di Marzo N., Chisci E., Giovannoni R. The Role of Hydrogen Peroxide in Redox-Dependent Signaling: Homeostatic and Pathological Responses in Mammalian Cells. Cells. 2018;7:156. doi: 10.3390/cells7100156. PubMed DOI PMC

Jang H.H., Lee K.O., Chi Y.H., Jung B.G., Park S.K., Park J.H., Lee J.R., Lee S.S., Moon J.C., Yun J.W., et al. Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell. 2004;117:625–635. doi: 10.1016/j.cell.2004.05.002. PubMed DOI

Neumann C.A., Cao J., Manevich Y. Peroxiredoxin 1 and its role in cell signaling. Cell Cycle Georget. Tex. 2009;8:4072–4078. doi: 10.4161/cc.8.24.10242. PubMed DOI PMC

Stocker S., Van Laer K., Mijuskovic A., Dick T.P. The Conundrum of Hydrogen Peroxide Signaling and the Emerging Role of Peroxiredoxins as Redox Relay Hubs. Antioxid. Redox Signal. 2018;28:558–573. doi: 10.1089/ars.2017.7162. PubMed DOI

Rhee S.G., Woo H.A., Kang D. The Role of Peroxiredoxins in the Transduction of H2O2 Signals. Antioxid. Redox Signal. 2018;28:537–557. doi: 10.1089/ars.2017.7167. PubMed DOI

Sobotta M.C., Liou W., Stocker S., Talwar D., Oehler M., Ruppert T., Scharf A.N., Dick T.P. Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat. Chem. Biol. 2015;11:64–70. doi: 10.1038/nchembio.1695. PubMed DOI

Jarvis R.M., Hughes S.M., Ledgerwood E.C. Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free Radic. Biol. Med. 2012;53:1522–1530. doi: 10.1016/j.freeradbiomed.2012.08.001. PubMed DOI

Stocker S., Maurer M., Ruppert T., Dick T.P. A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation. Nat. Chem. Biol. 2018;14:148–155. doi: 10.1038/nchembio.2536. PubMed DOI PMC

Go Y.M., Roede J.R., Walker D.I., Duong D.M., Seyfried N.T., Orr M., Liang Y., Pennell K.D., Jones D.P. Selective targeting of the cysteine proteome by thioredoxin and glutathione redox systems. Mol. Cell. Proteom. MCP. 2013;12:3285–3296. doi: 10.1074/mcp.M113.030437. PubMed DOI PMC

Soga M., Matsuzawa A., Ichijo H. Oxidative Stress-Induced Diseases via the ASK1 Signaling Pathway. Int. J. Cell Biol. 2012;2012:439587. doi: 10.1155/2012/439587. PubMed DOI PMC

Hsieh C.C., Papaconstantinou J. Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived Snell dwarf mice. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2006;20:259–268. doi: 10.1096/fj.05-4376com. PubMed DOI PMC

Tavender T.J., Springate J.J., Bulleid N.J. Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum. EMBO J. 2010;29:4185–4197. doi: 10.1038/emboj.2010.273. PubMed DOI PMC

Wei P.C., Hsieh Y.H., Su M.I., Jiang X., Hsu P.H., Lo W.T., Weng J.Y., Jeng Y.M., Wang J.M., Chen P.L., et al. Loss of the oxidative stress sensor NPGPx compromises GRP78 chaperone activity and induces systemic disease. Mol. Cell. 2012;48:747–759. doi: 10.1016/j.molcel.2012.10.007. PubMed DOI PMC

Cao Z., Lindsay J.G., Isaacs N.W. Mitochondrial peroxiredoxins. Sub. Cell. Biochem. 2007;44:295–315. doi: 10.1007/978-1-4020-6051-9_14. PubMed DOI

Seo M.S., Kang S.W., Kim K., Baines I.C., Lee T.H., Rhee S.G. Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate. J. Biol. Chem. 2000;275:20346–20354. doi: 10.1074/jbc.M001943200. PubMed DOI

Kropotov A., Usmanova N., Serikov V., Zhivotovsky B., Tomilin N. Mitochondrial targeting of human peroxiredoxin V protein and regulation of PRDX5 gene expression by nuclear transcription factors controlling biogenesis of mitochondria. FEBS J. 2007;274:5804–5814. doi: 10.1111/j.1742-4658.2007.06103.x. PubMed DOI

Brigelius-Flohe R., Maiorino M. Glutathione peroxidases. Biochim. Biophys. Acta. 2013;1830:3289–3303. doi: 10.1016/j.bbagen.2012.11.020. PubMed DOI

Ighodaro O.M., Akinloye O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med. 2018;54:287–293. doi: 10.1016/j.ajme.2017.09.001. DOI

Herbette S., Roeckel-Drevet P., Drevet J.R. Seleno-independent glutathione peroxidases. More than simple antioxidant scavengers. FEBS J. 2007;274:2163–2180. doi: 10.1111/j.1742-4658.2007.05774.x. PubMed DOI

Dikalov S. Cross talk between mitochondria and NADPH oxidases. Free Radic. Biol. Med. 2011;51:1289–1301. doi: 10.1016/j.freeradbiomed.2011.06.033. PubMed DOI PMC

Archer S.L., Marsboom G., Kim G.H., Zhang H.J., Toth P.T., Svensson E.C., Dyck J.R., Gomberg-Maitland M., Thebaud B., Husain A.N., et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: A basis for excessive cell proliferation and a new therapeutic target. Circulation. 2010;121:2661–2671. doi: 10.1161/CIRCULATIONAHA.109.916098. PubMed DOI PMC

Doughan A.K., Harrison D.G., Dikalov S.I. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: Linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ. Res. 2008;102:488–496. doi: 10.1161/CIRCRESAHA.107.162800. PubMed DOI

Salazar G. NADPH Oxidases and Mitochondria in Vascular Senescence. Int. J. Mol. Sci. 2018;19:1327. doi: 10.3390/ijms19051327. PubMed DOI PMC

Xiong S., Salazar G., San Martin A., Ahmad M., Patrushev N., Hilenski L., Nazarewicz R.R., Ma M., Ushio-Fukai M., Alexander R.W. PGC-1 alpha serine 570 phosphorylation and GCN5-mediated acetylation by angiotensin II drive catalase down-regulation and vascular hypertrophy. J. Biol. Chem. 2010;285:2474–2487. doi: 10.1074/jbc.M109.065235. PubMed DOI PMC

Mistry Y., Poolman T., Williams B., Herbert K.E. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells. Redox Biol. 2013;1:411–417. doi: 10.1016/j.redox.2013.08.004. PubMed DOI PMC

Daiber A., Di Lisa F., Oelze M., Kroller-Schon S., Steven S., Schulz E., Munzel T. Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function. Br. J. Pharmacol. 2017;174:1670–1689. doi: 10.1111/bph.13403. PubMed DOI PMC

Salazar G., Huang J., Feresin R.G., Zhao Y., Griendling K.K. Zinc regulates Nox1 expression through a NF-kappaB and mitochondrial ROS dependent mechanism to induce senescence of vascular smooth muscle cells. Free Radic. Biol. Med. 2017;108:225–235. doi: 10.1016/j.freeradbiomed.2017.03.032. PubMed DOI

Appelhoff R.J., Tian Y.M., Raval R.R., Turley H., Harris A.L., Pugh C.W., Ratcliffe P.J., Gleadle J.M. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J. Biol. Chem. 2004;279:38458–38465. doi: 10.1074/jbc.M406026200. PubMed DOI

Lu H., Dalgard C.L., Mohyeldin A., McFate T., Tait A.S., Verma A. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J. Biol. Chem. 2005;280:41928–41939. doi: 10.1074/jbc.M508718200. PubMed DOI

Gerald D., Berra E., Frapart Y.M., Chan D.A., Giaccia A.J., Mansuy D., Pouyssegur J., Yaniv M., Mechta-Grigoriou F. JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell. 2004;118:781–794. doi: 10.1016/j.cell.2004.08.025. PubMed DOI

Briggs K.J., Koivunen P., Cao S., Backus K.M., Olenchock B.A., Patel H., Zhang Q., Signoretti S., Gerfen G.J., Richardson A.L., et al. Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016;166:126–139. doi: 10.1016/j.cell.2016.05.042. PubMed DOI PMC

Lee G., Won H.S., Lee Y.M., Choi J.W., Oh T.I., Jang J.H., Choi D.K., Lim B.O., Kim Y.J., Park J.W., et al. Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1alpha Activation. Sci. Rep. 2016;6:18928. doi: 10.1038/srep18928. PubMed DOI PMC

Chowdhury R., Flashman E., Mecinovic J., Kramer H.B., Kessler B.M., Frapart Y.M., Boucher J.L., Clifton I.J., McDonough M.A., Schofield C.J. Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1) J. Mol. Biol. 2011;410:268–279. doi: 10.1016/j.jmb.2011.04.075. PubMed DOI

Ivan M., Kondo K., Yang H., Kim W., Valiando J., Ohh M., Salic A., Asara J.M., Lane W.S., Kaelin W.G., Jr. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Sci. N. Y. 2001;292:464–468. doi: 10.1126/science.1059817. PubMed DOI

Jaakkola P., Mole D.R., Tian Y.M., Wilson M.I., Gielbert J., Gaskell S.J., von Kriegsheim A., Hebestreit H.F., Mukherji M., Schofield C.J., et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Sci. N. Y. 2001;292:468–472. doi: 10.1126/science.1059796. PubMed DOI

Schodel J., Oikonomopoulos S., Ragoussis J., Pugh C.W., Ratcliffe P.J., Mole D.R. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood. 2011;117:e207–e217. doi: 10.1182/blood-2010-10-314427. PubMed DOI PMC

Brocato J., Chervona Y., Costa M. Molecular responses to hypoxia-inducible factor 1alpha and beyond. Mol. Pharmacol. 2014;85:651–657. doi: 10.1124/mol.113.089623. PubMed DOI PMC

Kim J.W., Tchernyshyov I., Semenza G.L., Dang C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–185. doi: 10.1016/j.cmet.2006.02.002. PubMed DOI

Fukuda R., Zhang H., Kim J.W., Shimoda L., Dang C.V., Semenza G.L. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell. 2007;129:111–122. doi: 10.1016/j.cell.2007.01.047. PubMed DOI

Semenza G.L. Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem. J. 2007;405:1–9. doi: 10.1042/BJ20070389. PubMed DOI

Semenza G.L. Regulation of metabolism by hypoxia-inducible factor 1. Cold Spring Harb. Symp. Quant. Biol. 2011;76:347–353. doi: 10.1101/sqb.2011.76.010678. PubMed DOI

Pan Y., Mansfield K.D., Bertozzi C.C., Rudenko V., Chan D.A., Giaccia A.J., Simon M.C. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol. Cell. Biol. 2007;27:912–925. doi: 10.1128/MCB.01223-06. PubMed DOI PMC

Hewitson K.S., Lienard B.M., McDonough M.A., Clifton I.J., Butler D., Soares A.S., Oldham N.J., McNeill L.A., Schofield C.J. Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates. J. Biol. Chem. 2007;282:3293–3301. doi: 10.1074/jbc.M608337200. PubMed DOI

Koivunen P., Hirsila M., Remes A.M., Hassinen I.E., Kivirikko K.I., Myllyharju J. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: Possible links between cell metabolism and stabilization of HIF. J. Biol. Chem. 2007;282:4524–4532. doi: 10.1074/jbc.M610415200. PubMed DOI

Martinez-Reyes I., Diebold L.P., Kong H., Schieber M., Huang H., Hensley C.T., Mehta M.M., Wang T., Santos J.H., Woychik R., et al. TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions. Mol. Cell. 2016;61:199–209. doi: 10.1016/j.molcel.2015.12.002. PubMed DOI PMC

Isaacs J.S., Jung Y.J., Mole D.R., Lee S., Torres-Cabala C., Chung Y.L., Merino M., Trepel J., Zbar B., Toro J., et al. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005;8:143–153. doi: 10.1016/j.ccr.2005.06.017. PubMed DOI

Selak M.A., Armour S.M., MacKenzie E.D., Boulahbel H., Watson D.G., Mansfield K.D., Pan Y., Simon M.C., Thompson C.B., Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005;7:77–85. doi: 10.1016/j.ccr.2004.11.022. PubMed DOI

Burr S.P., Costa A.S., Grice G.L., Timms R.T., Lobb I.T., Freisinger P., Dodd R.B., Dougan G., Lehner P.J., Frezza C., et al. Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls HIF1alpha Stability in Aerobic Conditions. Cell Metab. 2016;24:740–752. doi: 10.1016/j.cmet.2016.09.015. PubMed DOI PMC

Wen Y.A., Xiong X., Scott T., Li A.T., Wang C., Weiss H.L., Tan L., Bradford E., Fan T.W.M., Chandel N.S., et al. The mitochondrial retrograde signaling regulates Wnt signaling to promote tumorigenesis in colon cancer. Cell Death Differ. 2019;26:1955–1969. doi: 10.1038/s41418-018-0265-6. PubMed DOI PMC

Zhang H., Bosch-Marce M., Shimoda L.A., Tan Y.S., Baek J.H., Wesley J.B., Gonzalez F.J., Semenza G.L. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J. Biol. Chem. 2008;283:10892–10903. doi: 10.1074/jbc.M800102200. PubMed DOI PMC

Bell E.L., Klimova T.A., Eisenbart J., Moraes C.T., Murphy M.P., Budinger G.R., Chandel N.S. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J. Cell Biol. 2007;177:1029–1036. doi: 10.1083/jcb.200609074. PubMed DOI PMC

Plecitá-Hlavatá L., Ježek J., Ježek P. Aglycemia keeps mitochondrial oxidative phosphorylation under hypoxic conditions in HepG2 cells. J. Bioenerg. Biomembr. 2015;47:467–476. doi: 10.1007/s10863-015-9628-6. PubMed DOI

Nguyen L.K., Cavadas M.A., Scholz C.C., Fitzpatrick S.F., Bruning U., Cummins E.P., Tambuwala M.M., Manresa M.C., Kholodenko B.N., Taylor C.T., et al. A dynamic model of the hypoxia-inducible factor 1alpha (HIF-1alpha) network. J. Cell Sci. 2013;126:1454–1463. doi: 10.1242/jcs.119974. PubMed DOI

Hernansanz-Agustin P., Ramos E., Navarro E., Parada E., Sanchez-Lopez N., Pelaez-Aguado L., Cabrera-Garcia J.D., Tello D., Buendia I., Marina A., et al. Mitochondrial complex I deactivation is related to superoxide production in acute hypoxia. Redox Biol. 2017;12:1040–1051. doi: 10.1016/j.redox.2017.04.025. PubMed DOI PMC

Chandel N.S., Maltepe E., Goldwasser E., Mathieu C.E., Simon M.C., Schumacker P.T. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA. 1998;95:11715–11720. doi: 10.1073/pnas.95.20.11715. PubMed DOI PMC

Schroedl C., McClintock D.S., Budinger G.R., Chandel N.S. Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Am. J. Physiol. Lung Cell. Mol. Physiol. 2002;283:L922–L931. doi: 10.1152/ajplung.00014.2002. PubMed DOI

Guzy R.D., Hoyos B., Robin E., Chen H., Liu L., Mansfield K.D., Simon M.C., Hammerling U., Schumacker P.T. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 2005;1:401–408. doi: 10.1016/j.cmet.2005.05.001. PubMed DOI

Waypa G.B., Marks J.D., Guzy R., Mungai P.T., Schriewer J., Dokic D., Schumacker P.T. Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells. Circ. Res. 2010;106:526–535. doi: 10.1161/CIRCRESAHA.109.206334. PubMed DOI PMC

Comito G., Calvani M., Giannoni E., Bianchini F., Calorini L., Torre E., Migliore C., Giordano S., Chiarugi P. HIF-1alpha stabilization by mitochondrial ROS promotes Met-dependent invasive growth and vasculogenic mimicry in melanoma cells. Free Radic. Biol. Med. 2011;51:893–904. doi: 10.1016/j.freeradbiomed.2011.05.042. PubMed DOI

Sabharwal S.S., Waypa G.B., Marks J.D., Schumacker P.T. Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling. Biochem. J. 2013;456:337–346. doi: 10.1042/BJ20130740. PubMed DOI PMC

Patten D.A., Lafleur V.N., Robitaille G.A., Chan D.A., Giaccia A.J., Richard D.E. Hypoxia-inducible factor-1 activation in nonhypoxic conditions: The essential role of mitochondrial-derived reactive oxygen species. Mol. Biol. Cell. 2010;21:3247–3257. doi: 10.1091/mbc.e10-01-0025. PubMed DOI PMC

Orr A.L., Vargas L., Turk C.N., Baaten J.E., Matzen J.T., Dardov V.J., Attle S.J., Li J., Quackenbush D.C., Goncalves R.L., et al. Suppressors of superoxide production from mitochondrial complex III. Nat. Chem. Biol. 2015;11:834–836. doi: 10.1038/nchembio.1910. PubMed DOI PMC

Jezek P., Plecita-Hlavata L. Mitochondrial reticulum network dynamics in relation to oxidative stress, redox regulation, and hypoxia. Int. J. Biochem. Cell Biol. 2009;41:1790–1804. doi: 10.1016/j.biocel.2009.02.014. PubMed DOI

Yue X., Zhao P., Wu K., Huang J., Zhang W., Wu Y., Liang X., He X. GRIM-19 inhibition induced autophagy through activation of ERK and HIF-1alpha not STAT3 in Hela cells. Tumour Biol. J. Int. Soc. Oncodev. Biol. Med. 2016;37:9789–9796. doi: 10.1007/s13277-016-4877-5. PubMed DOI

Guzy R.D., Sharma B., Bell E., Chandel N.S., Schumacker P.T. Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol. Cell. Biol. 2008;28:718–731. doi: 10.1128/MCB.01338-07. PubMed DOI PMC

Saito Y., Ishii K.A., Aita Y., Ikeda T., Kawakami Y., Shimano H., Hara H., Takekoshi K. Loss of SDHB Elevates Catecholamine Synthesis and Secretion Depending on ROS Production and HIF Stabilization. Neurochem. Res. 2016;41:696–706. doi: 10.1007/s11064-015-1738-3. PubMed DOI

Diaz F., Enriquez J.A., Moraes C.T. Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV. Mol. Cell. Biol. 2012;32:415–429. doi: 10.1128/MCB.06051-11. PubMed DOI PMC

Bastian A., Matsuzaki S., Humphries K.M., Pharaoh G.A., Doshi A., Zaware N., Gangjee A., Ihnat M.A. AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1alpha stabilization. Cancer Lett. 2017;388:149–157. doi: 10.1016/j.canlet.2016.11.040. PubMed DOI PMC

Tello D., Balsa E., Acosta-Iborra B., Fuertes-Yebra E., Elorza A., Ordonez A., Corral-Escariz M., Soro I., Lopez-Bernardo E., Perales-Clemente E., et al. Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity. Cell Metab. 2011;14:768–779. doi: 10.1016/j.cmet.2011.10.008. PubMed DOI

Lai R.K., Xu I.M., Chiu D.K., Tse A.P., Wei L.L., Law C.T., Lee D., Wong C.M., Wong M.P., Ng I.O., et al. NDUFA4L2 Fine-tunes Oxidative Stress in Hepatocellular Carcinoma. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2016;22:3105–3117. doi: 10.1158/1078-0432.CCR-15-1987. PubMed DOI

Guaras A., Perales-Clemente E., Calvo E., Acin-Perez R., Loureiro-Lopez M., Pujol C., Martinez-Carrascoso I., Nunez E., Garcia-Marques F., Rodriguez-Hernandez M.A., et al. The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency. Cell Rep. 2016;15:197–209. doi: 10.1016/j.celrep.2016.03.009. PubMed DOI

Zuo L., Pannell B.K. Redox Characterization of Functioning Skeletal Muscle. Front. Physiol. 2015;6:338. doi: 10.3389/fphys.2015.00338. PubMed DOI PMC

Wu H., Kanatous S.B., Thurmond F.A., Gallardo T., Isotani E., Bassel-Duby R., Williams R.S. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Sci. N. Y. 2002;296:349–352. doi: 10.1126/science.1071163. PubMed DOI

Gowans G.J., Hawley S.A., Ross F.A., Hardie D.G. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 2013;18:556–566. doi: 10.1016/j.cmet.2013.08.019. PubMed DOI PMC

Pogozelski A.R., Geng T., Li P., Yin X., Lira V.A., Zhang M., Chi J.T., Yan Z. p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice. PLoS ONE. 2009;4:e7934. doi: 10.1371/journal.pone.0007934. PubMed DOI PMC

Irrcher I., Ljubicic V., Hood D.A. Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells. Am. J. Physiol. Cell Physiol. 2009;296:C116–C123. doi: 10.1152/ajpcell.00267.2007. PubMed DOI

Powers S.K., Talbert E.E., Adhihetty P.J. Reactive oxygen and nitrogen species as intracellular signals in skeletal muscle. J. Physiol. 2011;589:2129–2138. doi: 10.1113/jphysiol.2010.201327. PubMed DOI PMC

Saleem A., Hood D.A. Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53-Tfam-mitochondrial DNA complex in skeletal muscle. J. Physiol. 2013;591:3625–3636. doi: 10.1113/jphysiol.2013.252791. PubMed DOI PMC

Picard M., Gentil B.J., McManus M.J., White K., St Louis K., Gartside S.E., Wallace D.C., Turnbull D.M. Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle. J. Appl. Physiol. 2013;115:1562–1571. doi: 10.1152/japplphysiol.00819.2013. PubMed DOI PMC

Mishra P., Varuzhanyan G., Pham A.H., Chan D.C. Mitochondrial Dynamics is a Distinguishing Feature of Skeletal Muscle Fiber Types and Regulates Organellar Compartmentalization. Cell Metab. 2015;22:1033–1044. doi: 10.1016/j.cmet.2015.09.027. PubMed DOI PMC

Porter C., Reidy P.T., Bhattarai N., Sidossis L.S., Rasmussen B.B. Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle. Med. Sci. Sports Exerc. 2015;47:1922–1931. doi: 10.1249/MSS.0000000000000605. PubMed DOI PMC

Nielsen J., Gejl K.D., Hey-Mogensen M., Holmberg H.C., Suetta C., Krustrup P., Elemans C.P.H., Ortenblad N. Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle. J. Physiol. 2017;595:2839–2847. doi: 10.1113/JP273040. PubMed DOI PMC

Holloway G.P. Nutrition and Training Influences on the Regulation of Mitochondrial Adenosine Diphosphate Sensitivity and Bioenergetics. Sports Med. 2017;47:13–21. doi: 10.1007/s40279-017-0693-3. PubMed DOI PMC

Dahl R., Larsen S., Dohlmann T.L., Qvortrup K., Helge J.W., Dela F., Prats C. Three-dimensional reconstruction of the human skeletal muscle mitochondrial network as a tool to assess mitochondrial content and structural organization. Acta Physiol. 2015;213:145–155. doi: 10.1111/apha.12289. PubMed DOI

Glancy B., Hartnell L.M., Combs C.A., Femnou A., Sun J., Murphy E., Subramaniam S., Balaban R.S. Power Grid Protection of the Muscle Mitochondrial Reticulum. Cell Rep. 2017;19:487–496. doi: 10.1016/j.celrep.2017.03.063. PubMed DOI PMC

Picard M., White K., Turnbull D.M. Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: A quantitative three-dimensional electron microscopy study. J. Appl. Physiol. 2013;114:161–171. doi: 10.1152/japplphysiol.01096.2012. PubMed DOI PMC

Iqbal S., Hood D.A. Cytoskeletal regulation of mitochondrial movements in myoblasts. Cytoskelet. 2014;71:564–572. doi: 10.1002/cm.21188. PubMed DOI

Goncalves R.L.S., Watson M.A., Wong H.S., Orr A.L., Brand M.D. The use of site-specific suppressors to measure the relative contributions of different mitochondrial sites to skeletal muscle superoxide and hydrogen peroxide production. Redox Biol. 2019;28:101341. doi: 10.1016/j.redox.2019.101341. PubMed DOI PMC

Ježek P., Jabůrek M., Holendová B., Plecitá-Hlavatá L. Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity. Molecules. 2018;23:1483. doi: 10.3390/molecules23061483. PubMed DOI PMC

Prentki M., Matschinsky F.M., Madiraju S.R.M. Metabolic Signaling in Fuel-Induced Insulin Secretion. Cell Metab. 2013;18:162–185. doi: 10.1016/j.cmet.2013.05.018. PubMed DOI

Carpinelli A.R., Picinato M.C., Stevanato E., Oliveira H.R., Curi R. Insulin secretion induced by palmitate--a process fully dependent on glucose concentration. Diabetes Metab. 2002;28:S37–S44. PubMed

Gehrmann W., Elsner M., Lenzen S. Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic β-cells. DiabetesObes. Metab. 2010;12:149–158. doi: 10.1111/j.1463-1326.2010.01265.x. PubMed DOI

Graciano M.F.R., Valle M.M.R., Kowluru A., Curi R., Carpinelli A.R. Regulation of insulin secretion and reactive oxygen species production by free fatty acids in pancreatic islets. Islets. 2011;3:213–223. doi: 10.4161/isl.3.5.15935. PubMed DOI

Cen J., Sargsyan E., Bergsten P. Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms. Nutr. Metab. 2016;13:59. doi: 10.1186/s12986-016-0119-5. PubMed DOI PMC

Itoh Y., Kawamata Y., Harada M., Kobayashi M., Fujii R., Fukusumi S., Ogi K., Hosoya M., Tanaka Y., Uejima H., et al. Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40. Nature. 2003;422:173–176. doi: 10.1038/nature01478. PubMed DOI

Latour M.G., Alquier T., Oseid E., Tremblay C., Jetton T.L., Luo J., Lin D.C., Poitout V. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes. 2007;56:1087–1094. doi: 10.2337/db06-1532. PubMed DOI PMC

Sabrautzki S., Kaiser G., Przemeck G.K.H., Gerst F., Lorza-Gil E., Panse M., Sartorius T., Hoene M., Marschall S., Haring H.U., et al. Point mutation of Ffar1 abrogates fatty acid-dependent insulin secretion, but protects against HFD-induced glucose intolerance. Mol. Metab. 2017;6:1304–1312. doi: 10.1016/j.molmet.2017.07.007. PubMed DOI PMC

Hauge M., Vestmar M.A., Husted A.S., Ekberg J.P., Wright M.J., Di Salvo J., Weinglass A.B., Engelstoft M.S., Madsen A.N., Luckmann M., et al. GPR40 (FFAR1)—Combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo. Mol. Metab. 2015;4:3–14. doi: 10.1016/j.molmet.2014.10.002. PubMed DOI PMC

Qian J., Gu Y., Wu C., Yu F., Chen Y., Zhu J., Yao X., Bei C., Zhu Q. Agonist-induced activation of human FFA1 receptor signals to extracellular signal-regulated kinase 1 and 2 through Gq- and Gi-coupled signaling cascades. Cell. Mol. Biol. Lett. 2017;22:13. doi: 10.1186/s11658-017-0043-3. PubMed DOI PMC

Husted A.S., Trauelsen M., Rudenko O., Hjorth S.A., Schwartz T.W. GPCR-Mediated Signaling of Metabolites. Cell Metab. 2017;25:777–796. doi: 10.1016/j.cmet.2017.03.008. PubMed DOI

Graciano M.F., Valle M.M., Curi R., Carpinelli A.R. Evidence for the involvement of GPR40 and NADPH oxidase in palmitic acid-induced superoxide production and insulin secretion. Islets. 2013;5:139–148. doi: 10.4161/isl.25459. PubMed DOI

Kristinsson H., Bergsten P., Sargsyan E. Free fatty acid receptor 1 (FFAR1/GPR40) signaling affects insulin secretion by enhancing mitochondrial respiration during palmitate exposure. Biochim. Biophys. Acta. 2015;1853:3248–3257. doi: 10.1016/j.bbamcr.2015.09.022. PubMed DOI

Duan Y., Li F., Li Y., Tang Y., Kong X., Feng Z., Anthony T.G., Watford M., Hou Y., Wu G., et al. The role of leucine and its metabolites in protein and energy metabolism. Amino Acids. 2016;48:41–51. doi: 10.1007/s00726-015-2067-1. PubMed DOI

Nicholas L.M., Valtat B., Medina A., Andersson L., Abels M., Mollet I.G., Jain D., Eliasson L., Wierup N., Fex M., et al. Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic beta-cells. Mol. Metab. 2017;6:651–663. doi: 10.1016/j.molmet.2017.05.005. PubMed DOI PMC

Benmoussa K., Garaude J., Acin-Perez R. How Mitochondrial Metabolism Contributes to Macrophage Phenotype and Functions. J. Mol. Biol. 2018;430:3906–3921. doi: 10.1016/j.jmb.2018.07.003. PubMed DOI

Ryan D.G., Murphy M.P., Frezza C., Prag H.A., Chouchani E.T., O’Neill L.A., Mills E.L. Coupling Krebs cycle metabolites to signalling in immunity and cancer. Nat. Metab. 2019;1:16–33. doi: 10.1038/s42255-018-0014-7. PubMed DOI PMC

Weinberg S.E., Singer B.D., Steinert E.M., Martinez C.A., Mehta M.M., Martinez-Reyes I., Gao P., Helmin K.A., Abdala-Valencia H., Sena L.A., et al. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature. 2019;565:495–499. doi: 10.1038/s41586-018-0846-z. PubMed DOI PMC

Mehta M.M., Weinberg S.E., Chandel N.S. Mitochondrial control of immunity: Beyond ATP. Nat. Rev. Immunol. 2017;17:608–620. doi: 10.1038/nri.2017.66. PubMed DOI

Kong H., Chandel N.S. Regulation of redox balance in cancer and T cells. J. Biol. Chem. 2018;293:7499–7507. doi: 10.1074/jbc.TM117.000257. PubMed DOI PMC

O’Neill L.A., Golenbock D., Bowie A.G. The history of Toll-like receptors—Redefining innate immunity. Nat. Rev. Immunol. 2013;13:453–460. doi: 10.1038/nri3446. PubMed DOI

Danielski L.G., Giustina A.D., Bonfante S., Barichello T., Petronilho F. The NLRP3 Inflammasome and Its Role in Sepsis Development. Inflammation. 2019 doi: 10.1007/s10753-019-01124-9. PubMed DOI

Kelley N., Jeltema D., Duan Y., He Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci. 2019;20:3328. doi: 10.3390/ijms20133328. PubMed DOI PMC

Osorio F., Reis e Sousa C. Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity. 2011;34:651–664. doi: 10.1016/j.immuni.2011.05.001. PubMed DOI

Brubaker S.W., Bonham K.S., Zanoni I., Kagan J.C. Innate immune pattern recognition: A cell biological perspective. Annu. Rev. Immunol. 2015;33:257–290. doi: 10.1146/annurev-immunol-032414-112240. PubMed DOI PMC

Chen Q., Sun L., Chen Z.J. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol. 2016;17:1142–1149. doi: 10.1038/ni.3558. PubMed DOI

Jha A.K., Huang S.C., Sergushichev A., Lampropoulou V., Ivanova Y., Loginicheva E., Chmielewski K., Stewart K.M., Ashall J., Everts B., et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015;42:419–430. doi: 10.1016/j.immuni.2015.02.005. PubMed DOI

Mills E.L., Ryan D.G., Prag H.A., Dikovskaya D., Menon D., Zaslona Z., Jedrychowski M.P., Costa A.S.H., Higgins M., Hams E., et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018;556:113–117. doi: 10.1038/nature25986. PubMed DOI PMC

Lampropoulou V., Sergushichev A., Bambouskova M., Nair S., Vincent E.E., Loginicheva E., Cervantes-Barragan L., Ma X., Huang S.C., Griss T., et al. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab. 2016;24:158–166. doi: 10.1016/j.cmet.2016.06.004. PubMed DOI PMC

Sonoda J., Laganiere J., Mehl I.R., Barish G.D., Chong L.W., Li X., Scheffler I.E., Mock D.C., Bataille A.R., Robert F., et al. Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Genes Dev. 2007;21:1909–1920. doi: 10.1101/gad.1553007. PubMed DOI PMC

West A.P., Brodsky I.E., Rahner C., Woo D.K., Erdjument-Bromage H., Tempst P., Walsh M.C., Choi Y., Shadel G.S., Ghosh S. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature. 2011;472:476–480. doi: 10.1038/nature09973. PubMed DOI PMC

Rousset S., Emre Y., Join-Lambert O., Hurtaud C., Ricquier D., Cassard-Doulcier A.M. The uncoupling protein 2 modulates the cytokine balance in innate immunity. Cytokine. 2006;35:135–142. doi: 10.1016/j.cyto.2006.07.012. PubMed DOI

Bai Y., Onuma H., Bai X., Medvedev A.V., Misukonis M., Weinberg J.B., Cao W., Robidoux J., Floering L.M., Daniel K.W., et al. Persistent nuclear factor-kappa B activation in Ucp2-/- mice leads to enhanced nitric oxide and inflammatory cytokine production. J. Biol. Chem. 2005;280:19062–19069. doi: 10.1074/jbc.M500566200. PubMed DOI PMC

Iyer S.S., He Q., Janczy J.R., Elliott E.I., Zhong Z., Olivier A.K., Sadler J.J., Knepper-Adrian V., Han R., Qiao L., et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity. 2013;39:311–323. doi: 10.1016/j.immuni.2013.08.001. PubMed DOI PMC

Vazquez C., Horner S.M. MAVS Coordination of Antiviral Innate Immunity. J. Virol. 2015;89:6974–6977. doi: 10.1128/JVI.01918-14. PubMed DOI PMC

Moon J.S., Lee S., Park M.A., Siempos I.I., Haslip M., Lee P.J., Yun M., Kim C.K., Howrylak J., Ryter S.W., et al. UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis. J. Clin. Investig. 2015;125:665–680. doi: 10.1172/JCI78253. PubMed DOI PMC

Ma M.W., Wang J., Dhandapani K.M., Brann D.W. NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury. Oxidative Med. Cell. Longev. 2017;2017:6057609. doi: 10.1155/2017/6057609. PubMed DOI PMC

Moon J.S., Nakahira K., Chung K.P., DeNicola G.M., Koo M.J., Pabon M.A., Rooney K.T., Yoon J.H., Ryter S.W., Stout-Delgado H., et al. NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages. Nat. Med. 2016;22:1002–1012. doi: 10.1038/nm.4153. PubMed DOI PMC

Nakahira K., Haspel J.A., Rathinam V.A., Lee S.J., Dolinay T., Lam H.C., Englert J.A., Rabinovitch M., Cernadas M., Kim H.P., et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 2011;12:222–230. doi: 10.1038/ni.1980. PubMed DOI PMC

Wu J., Yan Z., Schwartz D.E., Yu J., Malik A.B., Hu G. Activation of NLRP3 inflammasome in alveolar macrophages contributes to mechanical stretch-induced lung inflammation and injury. J. Immunol. 2013;190:3590–3599. doi: 10.4049/jimmunol.1200860. PubMed DOI PMC

Shimada K., Crother T.R., Karlin J., Dagvadorj J., Chiba N., Chen S., Ramanujan V.K., Wolf A.J., Vergnes L., Ojcius D.M., et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–414. doi: 10.1016/j.immuni.2012.01.009. PubMed DOI PMC

Zhong Z., Liang S., Sanchez-Lopez E., He F., Shalapour S., Lin X.J., Wong J., Ding S., Seki E., Schnabl B., et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature. 2018;560:198–203. doi: 10.1038/s41586-018-0372-z. PubMed DOI PMC

Bae J.Y., Park H.H. Crystal structure of NALP3 protein pyrin domain (PYD) and its implications in inflammasome assembly. J. Biol. Chem. 2011;286:39528–39536. doi: 10.1074/jbc.M111.278812. PubMed DOI PMC

Ichinohe T., Yamazaki T., Koshiba T., Yanagi Y. Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after RNA virus infection. Proc. Natl. Acad. Sci. USA. 2013;110:17963–17968. doi: 10.1073/pnas.1312571110. PubMed DOI PMC

Droge W. Free radicals in the physiological control of cell function. Physiol. Rev. 2002;82:47–95. doi: 10.1152/physrev.00018.2001. PubMed DOI

Franchina D.G., Dostert C., Brenner D. Reactive Oxygen Species: Involvement in T Cell Signaling and Metabolism. Trends Immunol. 2018;39:489–502. doi: 10.1016/j.it.2018.01.005. PubMed DOI

Kaminski M.M., Roth D., Sass S., Sauer S.W., Krammer P.H., Gulow K. Manganese superoxide dismutase: A regulator of T cell activation-induced oxidative signaling and cell death. Biochim. Biophys. Acta. 2012;1823:1041–1052. doi: 10.1016/j.bbamcr.2012.03.003. PubMed DOI

Kaminski M.M., Sauer S.W., Kaminski M., Opp S., Ruppert T., Grigaravicius P., Grudnik P., Grone H.J., Krammer P.H., Gulow K. T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation. Cell Rep. 2012;2:1300–1315. doi: 10.1016/j.celrep.2012.10.009. PubMed DOI

Rashida Gnanaprakasam J.N., Wu R., Wang R. Metabolic Reprogramming in Modulating T Cell Reactive Oxygen Species Generation and Antioxidant Capacity. Front. Immunol. 2018;9:1075. doi: 10.3389/fimmu.2018.01075. PubMed DOI PMC

Previte D.M., O’Connor E.C., Novak E.A., Martins C.P., Mollen K.P., Piganelli J.D. Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation. PLoS ONE. 2017;12:e0175549. doi: 10.1371/journal.pone.0175549. PubMed DOI PMC

O’Sullivan D., van der Windt G.J.W., Huang S.C., Curtis J.D., Chang C.H., Buck M.D., Qiu J., Smith A.M., Lam W.Y., DiPlato L.M., et al. Memory CD8(+) T Cells Use Cell-Intrinsic Lipolysis to Support the Metabolic Programming Necessary for Development. Immunity. 2018;49:375–376. doi: 10.1016/j.immuni.2018.07.018. PubMed DOI PMC

Cui G., Staron M.M., Gray S.M., Ho P.C., Amezquita R.A., Wu J., Kaech S.M. IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity. Cell. 2015;161:750–761. doi: 10.1016/j.cell.2015.03.021. PubMed DOI PMC

Wofford J.A., Wieman H.L., Jacobs S.R., Zhao Y., Rathmell J.C. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood. 2008;111:2101–2111. doi: 10.1182/blood-2007-06-096297. PubMed DOI PMC

Angajala A., Lim S., Phillips J.B., Kim J.H., Yates C., You Z., Tan M. Diverse Roles of Mitochondria in Immune Responses: Novel Insights into Immuno-Metabolism. Front. Immunol. 2018;9:1605. doi: 10.3389/fimmu.2018.01605. PubMed DOI PMC

Jang K.J., Mano H., Aoki K., Hayashi T., Muto A., Nambu Y., Takahashi K., Itoh K., Taketani S., Nutt S.L., et al. Mitochondrial function provides instructive signals for activation-induced B-cell fates. Nat. Commun. 2015;6:6750. doi: 10.1038/ncomms7750. PubMed DOI PMC

Gutierrez J., Ballinger S.W., Darley-Usmar V.M., Landar A. Free radicals, mitochondria, and oxidized lipids: The emerging role in signal transduction in vascular cells. Circ. Res. 2006;99:924–932. doi: 10.1161/01.RES.0000248212.86638.e9. PubMed DOI

Garlid K.D., Costa A.D., Quinlan C.L., Pierre S.V., Dos Santos P. Cardioprotective signaling to mitochondria. J. Mol. Cell. Cardiol. 2009;46:858–866. doi: 10.1016/j.yjmcc.2008.11.019. PubMed DOI PMC

Corcoran A., Cotter T.G. Redox regulation of protein kinases. FEBS J. 2013;280:1944–1965. doi: 10.1111/febs.12224. PubMed DOI

Cosentino-Gomes D., Rocco-Machado N., Meyer-Fernandes J.R. Cell signaling through protein kinase C oxidation and activation. Int. J. Mol. Sci. 2012;13:10697–10721. doi: 10.3390/ijms130910697. PubMed DOI PMC

Garlid A.O., Jaburek M., Jacobs J.P., Garlid K.D. Mitochondrial reactive oxygen species: Which ROS signals cardioprotection? Am. J. Physiol. Heart Circ. Physiol. 2013;305:H960–H968. doi: 10.1152/ajpheart.00858.2012. PubMed DOI PMC

Giorgi C., Agnoletto C., Baldini C., Bononi A., Bonora M., Marchi S., Missiroli S., Patergnani S., Poletti F., Rimessi A., et al. Redox control of protein kinase C: Cell- and disease-specific aspects. Antioxid. Redox Signal. 2010;13:1051–1085. doi: 10.1089/ars.2009.2825. PubMed DOI

Gopalakrishna R., Jaken S. Protein kinase C signaling and oxidative stress. Free Radic. Biol. Med. 2000;28:1349–1361. doi: 10.1016/S0891-5849(00)00221-5. PubMed DOI

Konishi H., Yamauchi E., Taniguchi H., Yamamoto T., Matsuzaki H., Takemura Y., Ohmae K., Kikkawa U., Nishizuka Y. Phosphorylation sites of protein kinase C delta in H2O2-treated cells and its activation by tyrosine kinase in vitro. Proc. Natl. Acad. Sci. USA. 2001;98:6587–6592. doi: 10.1073/pnas.111158798. PubMed DOI PMC

Rybin V.O., Guo J., Sabri A., Elouardighi H., Schaefer E., Steinberg S.F. Stimulus-specific differences in protein kinase C delta localization and activation mechanisms in cardiomyocytes. J. Biol. Chem. 2004;279:19350–19361. doi: 10.1074/jbc.M311096200. PubMed DOI

Connor K.M., Subbaram S., Regan K.J., Nelson K.K., Mazurkiewicz J.E., Bartholomew P.J., Aplin A.E., Tai Y.T., Aguirre-Ghiso J., Flores S.C., et al. Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation. J. Biol. Chem. 2005;280:16916–16924. doi: 10.1074/jbc.M410690200. PubMed DOI

Kimura S., Zhang G.X., Nishiyama A., Shokoji T., Yao L., Fan Y.Y., Rahman M., Abe Y. Mitochondria-derived reactive oxygen species and vascular MAP kinases: Comparison of angiotensin II and diazoxide. Hypertension. 2005;45:438–444. doi: 10.1161/01.HYP.0000157169.27818.ae. PubMed DOI

Nejnovějších 20 citací...

Zobrazit více v
Medvik | PubMed

Mitochondria to plasma membrane redox signaling is essential for fatty acid β-oxidation-driven insulin secretion

. 2024 Sep ; 75 () : 103283. [epub] 20240723

Mitochondrial Physiology of Cellular Redox Regulations

. 2024 Aug 30 ; 73 (S1) : S217-S242. [epub] 20240422

Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology

. 2023 Oct ; 39 (10-12) : 635-683. [epub] 20230411

Pitfalls of Mitochondrial Redox Signaling Research

. 2023 Aug 31 ; 12 (9) : . [epub] 20230831

Contribution of Mitochondria to Insulin Secretion by Various Secretagogues

. 2022 May ; 36 (13-15) : 920-952. [epub] 20210824

Antioxidant Role and Cardiolipin Remodeling by Redox-Activated Mitochondrial Ca2+-Independent Phospholipase A2γ in the Brain

. 2022 Jan 20 ; 11 (2) : . [epub] 20220120

Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid-Conducting SLC25 Gene Family Transporters

. 2021 Apr 26 ; 10 (5) : . [epub] 20210426

The Pancreatic β-Cell: The Perfect Redox System

. 2021 Jan 29 ; 10 (2) : . [epub] 20210129

Glucose-Stimulated Insulin Secretion Fundamentally Requires H2O2 Signaling by NADPH Oxidase 4

. 2020 Jul ; 69 (7) : 1341-1354. [epub] 20200403

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...