The present review is an attempt to conceptualize a contemporary understanding about the roles that cardiolipin, a mitochondrial specific conical phospholipid, and non-bilayer structures, predominantly found in the inner mitochondrial membrane (IMM), play in mitochondrial bioenergetics. This review outlines the link between changes in mitochondrial cardiolipin concentration and changes in mitochondrial bioenergetics, including changes in the IMM curvature and surface area, cristae density and architecture, efficiency of electron transport chain (ETC), interaction of ETC proteins, oligomerization of respiratory complexes, and mitochondrial ATP production. A relationship between cardiolipin decline in IMM and mitochondrial dysfunction leading to various diseases, including cardiovascular diseases, is thoroughly presented. Particular attention is paid to the targeting of cardiolipin by Szeto-Schiller tetrapeptides, which leads to rejuvenation of important mitochondrial activities in dysfunctional and aging mitochondria. The role of cardiolipin in triggering non-bilayer structures and the functional roles of non-bilayer structures in energy-converting membranes are reviewed. The latest studies on non-bilayer structures induced by cobra venom peptides are examined in model and mitochondrial membranes, including studies on how non-bilayer structures modulate mitochondrial activities. A mechanism by which non-bilayer compartments are formed in the apex of cristae and by which non-bilayer compartments facilitate ATP synthase dimerization and ATP production is also presented.

Bioenergetics Department Belozersky Research Institute for Physico Chemical Biology Lomonosov Moscow State University 119992 Moscow Russia

Biological Research Center H 6726 Szeged Hungary

Department of Physics Faculty of Science University of Ostrava 71000 Ostrava Czech Republic

Institute of Cytochemistry and Molecular Pharmacology 115404 Moscow Russia

Moscow Institute of Physics and Technology 141701 Dolgoprudny Russia

STEM Program Science Department Chaoyang KaiWen Academy Beijing 100018 China

Zobrazit více v PubMed

Szeto H.H., Liu S. Cardiolipin-targeted peptides rejuvenate mitochondrial function, remodel mitochondria, and promote tissue regeneration during aging. Arch. Biochem. Biophys. 2018;660:137–148. doi: 10.1016/j.abb.2018.10.013. PubMed DOI

Gomez L.A., Hagen T.M. Age-related decline in mitochondrial bioenergetics: Does supercomplex destabilization determine lower oxidative capacity and higher superoxide production? Semin. Cell Dev. Biol. 2012;23:758–767. doi: 10.1016/j.semcdb.2012.04.002. PubMed DOI PMC

Linnane A.W., Kovalenko S., Gingold E.B. The universality of bioenergetic 1 disease. Age associated cellular bioenergetic degradation and amelioration therapy. Ann. N. Y. Acad. Sci. 1998;854:202–213. doi: 10.1111/j.1749-6632.1998.tb09903.x. PubMed DOI

Sachs H.G., Colgan J.A., Lazarus M.L. Ultrastructure of the aging myocardium: An orphometric approach. Am. J. Anat. 1977;150:63–71. doi: 10.1002/aja.1001500105. PubMed DOI

Sato T., Tauchi H. Age changes of mitochondria of rat kidney. Mech. Ageing Dev. 1982;20:111–126. doi: 10.1016/0047-6374(82)90063-X. PubMed DOI

Savitha S., Panneerselvam C. Mitochondrial membrane damage during aging process in rat heart: Potential efficacy of L-carnitine and DL alpha lipoic acid. Mech. Ageing Dev. 2006;127:349–355. doi: 10.1016/j.mad.2005.12.004. PubMed DOI

Feher J., Kovacs I., Artico M., Cavallotti C., Papale A., Gabrieli C.B. Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol. Aging. 2006;27:983–993. doi: 10.1016/j.neurobiolaging.2005.05.012. PubMed DOI

Lenaz G., Bovina C., Castelluccio C., Fato R., Formiggini G., Genova M.L., Marchetti M., Pich M.M., Pallotti F., Castelli G.P., et al. Mitochondrial complex I defects in aging. Mol. Cell. Biochem. 1997;174:329–333. doi: 10.1023/A:1006854619336. PubMed DOI

Petrosillo G., Matera M., Casanova G., Ruggiero F.M., Paradies G. Mitochondrial dysfunction in rat brain with aging: Involvement of complex I, reactive oxygen species and cardiolipin. Neurochem. Int. 2008;53:126–131. doi: 10.1016/j.neuint.2008.07.001. PubMed DOI

Boveris A., Navarro A. Brain mitochondrial disfunction in aging. IUBMB Life. 2008;60:308–314. doi: 10.1002/iub.46. PubMed DOI

Navarro A., Boveris A. The mitochondrial energy transduction system and the aging process. Am. J. Physiol. Cell Physiol. 2007;292:670–686. doi: 10.1152/ajpcell.00213.2006. PubMed DOI

Miyoshi N., Oubrahim H., Chock P.B., Stadtman E.R. Age-dependent cell death and the role of ATP in hydrogen peroxide-induced apoptosis and necrosis. Proc. Natl. Acad. Sci. USA. 2006;103:1727–1731. doi: 10.1073/pnas.0510346103. PubMed DOI PMC

Hatch G.M. Cell biology of cardiac mitochondrial phospholipids. Biochem. Cell Biol. 2004;82:99–112. doi: 10.1139/o03-074. PubMed DOI

Schlame M., Greenberg M.L. Biosynthesis, remodeling and turnover of mitochondrial cardiolipin. Biochim. Biophys. Acta. 2017;1862:3–7. doi: 10.1016/j.bbalip.2016.08.010. PubMed DOI PMC

Boyd K.J., Alder N.N., May E.R. Buckling Under Pressure: Curvature-Based Lipid Segregation and Stability Modulation in Cardiolipin-Containing Bilayers. Langmuir. 2017;33:6937–6946. doi: 10.1021/acs.langmuir.7b01185. PubMed DOI PMC

Miranda-Díaz A.G., Cardona-Muñoz E.G., Paul Pacheco-Moisés F.P. The role of cardiolipin and mitochondrial damage in kidney transplant. Oxidative Med. Cell. Longev. 2019 doi: 10.1155/2019/3836186. PubMed DOI PMC

Schlame M., Ren M. The role of cardiolipin in the structural organization of mitochondrial membranes. Biochim. Biophys. Acta. 2009;1788:2080–2083. doi: 10.1016/j.bbamem.2009.04.019. PubMed DOI PMC

Musatov A., Sedlak E. Role of cardiolipin in stability of integral membrane proteins. Biochimie. 2017;142:102–111. doi: 10.1016/j.biochi.2017.08.013. PubMed DOI

Paradies G., Paradies V., Ruggiero F.M., Petrosillo G. Cardiolipin and mitochondrial function in health and disease. Antioxid. Redox Signal. 2014;20:1925–1953. doi: 10.1089/ars.2013.5280. PubMed DOI

Duncan A.L., Robinson A.J., Walker J.E. Cardiolipin binds selectively but transiently to conserved lysine residues in the rotor of metazoan ATP synthases. Proc. Natl. Acad. Sci. USA. 2016;113:8687–8692. doi: 10.1073/pnas.1608396113. PubMed DOI PMC

Strauss M., Hofhaus G., Schroder R.R., Kuhlbrandt W. Dimer ribbons of ATP synthase shape the inner mitochondrial membrane. EMBO J. 2008;27:1154–1160. doi: 10.1038/emboj.2008.35. PubMed DOI PMC

Davies K.M., Anselmi C., Wittig I., Faraldo-Gomez J.D., Kuhlbrandt W. 1 Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the mitochondrial cristae. Proc. Natl. Acad. Sci. USA. 2012;109:13602–13607. doi: 10.1073/pnas.1204593109. PubMed DOI PMC

Acehan D., Malhotra A., Xu Y., Ren M., Stokes D.L., Schlame M. Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria. Biophys. J. 2011;100:2184–2192. doi: 10.1016/j.bpj.2011.03.031. PubMed DOI PMC

Hahn A., Parey K., Bublitz M., Mills D.J., Zickermann V., Vonck J., Kühlbrandt W., Meier T. Structure of a complete ATP synthase dimer reveals the molecular basis of inner mitochondrial membrane morphology. Mol. Cell. 2016;63:445–456. doi: 10.1016/j.molcel.2016.05.037. PubMed DOI PMC

Zhang M., Mileykovskaya E., Dowhan W. Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane. J. Biol. Chem. 2002;277:43553–43556. doi: 10.1074/jbc.C200551200. PubMed DOI

Wittig I., Schagger H. Supramolecular organization of ATP synthase and respiratory chain in mitochondrial membranes. Biochim. Biophys. Acta. 2009;1787:672–680. doi: 10.1016/j.bbabio.2008.12.016. PubMed DOI

Letts J.A., Fiedorczuk K., Sazanov L.A. The architecture of respiratory supercomplexes. Nature. 2016;537:644–648. doi: 10.1038/nature19774. PubMed DOI

Kuhlbrandt W. Structure and function of mitochondrial membrane protein complexes. BMC Biol. 2015;13:89. doi: 10.1186/s12915-015-0201-x. PubMed DOI PMC

Rytomaa M., Kinnunen P.K. Evidence for two distinct acidic phospholipid-1 binding sites in cytochrome c. J. Biol. Chem. 1994;269:1770–1774. doi: 10.1016/S0021-9258(17)42094-1. PubMed DOI

Haines T.H., Dencher N.A. Cardiolipin: A proton trap for oxidative phosphorylation. FEBS Lett. 2002;528:35–39. doi: 10.1016/S0014-5793(02)03292-1. PubMed DOI

Rampelt H., Zerbes R.M., van der Laan M., Pfanner N. Role of the mitochondrial contact site and cristae organizing system in membrane architecture and dynamics. Biochim. Biophys. Acta Mol. Cell Res. 2017;1864:737–746. doi: 10.1016/j.bbamcr.2016.05.020. PubMed DOI

Kocherginsky N. Acidic lipids, H+-ATPases, and mechanism of oxidative phosphorylation. Physico-chemical ideas 30 years after P. Mitchell’s Nobel prize award. Prog. Biophys. Mol. Biol. 2009;99:20–41. doi: 10.1016/j.pbiomolbio.2008.10.013. PubMed DOI

Haines T.H. Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: A hypothesis. Proc. Natl. Acad. Sci. USA. 1983;80:160–164. doi: 10.1073/pnas.80.1.160. PubMed DOI PMC

Gasanov S.E., Kim A.A., Dagda R.K. The possible role of nonbilayer structures in regulating ATP synthase activity in mitochondrial membranes. Biophysics. 2016;61:596–600. doi: 10.1134/S0006350916040084. PubMed DOI PMC

Gasanov S.E., Kim A.A., Yaguzhinsky L.S., Dagda R.K. Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity. Biophys. Biochem. Acta Biomembr. 2018;1860:586–599. doi: 10.1016/j.bbamem.2017.11.014. PubMed DOI PMC

Gasanov S.E., Kim A.A., Dagda R.K. Possible role of nonbilayer structures in regulating the activity of ATP synthase in mitochondria. Biofizika. 2016;61:705–710. PubMed PMC

Li F., Shivastava I.H., Hanlon P., Dagda R.K., Gasanoff E.S. Molecular mechanism by which cobra venom cardiotoxin interact with the outer mitochondrial membrane. Toxins. 2020;12:425. doi: 10.3390/toxins12070425. PubMed DOI PMC

Azzone G.F., Colonna R., Ziche B. Preparation of bovine heart mitochondria in high yield. Methods Enzymol. 1979;55:46–50. PubMed

Maack C., O’Rourke B. Excitation-contraction coupling and mitochondrial energetics. Basic Res. Cardiol. 2007;102:369–392. doi: 10.1007/s00395-007-0666-z. PubMed DOI PMC

Shen Z., Ye C., McCain K., Greenberg M.I. The role of cardiolipin in cardiovascular health. BioMed Res. Int. 2015 doi: 10.1155/2015/891707. PubMed DOI PMC

Musatov A. Contribution of peroxidized cardiolipin to inactivation of bovine heart cytochrome c oxidase. Free Radic. Biol. Med. 2006;41:238–246. doi: 10.1016/j.freeradbiomed.2006.03.018. PubMed DOI

Zhang M., Mileykovskaya E., Dowhan W. Cardiolipin is essential for organization of complexes III and IV into a supercomplex in intact yeast mitochondria. J. Biol. Chem. 2005;280:29403–29408. doi: 10.1074/jbc.M504955200. PubMed DOI PMC

McKenzie M., Lazarou M., Thorburn D.R., Ryan M.T. Mitochondrial respiratory chain supercomplexes are destabilized in Barth syndrome patients. J. Mol. Biol. 2006;361:462–469. doi: 10.1016/j.jmb.2006.06.057. PubMed DOI

Kadenbach B., Mende P., Kolbe H.V.J., Stipani I., Palmieri F. Themitochondrial phosphate carrier has an essential requirement for cardiolipin. FEBS Lett. 1982;139:109–112. doi: 10.1016/0014-5793(82)80498-5. PubMed DOI

Paradies G., Ruggiero F.M. The effect of doxorubicin on the transport of pyruvate in rat-heart mitochondria. Biochem. Biophys. Res. Commun. 1988;156:1302–1307. doi: 10.1016/S0006-291X(88)80774-5. PubMed DOI

Beyer K., Klingenberg M. ADP/ATP carrier protein from beef heart mitochondria has high amounts of tightly bound cardiolipin, as revealed by 31P nuclear magnetic resonance. Biochemistry. 1985;24:3821–3826. doi: 10.1021/bi00336a001. PubMed DOI

Chen R., Tsuji T., Ichida F., Bowles K.R., Yu X., Watanabe S., Hirono K., Tsubata S., Hamamichi Y., Ohta J., et al. Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction. Mol. Genet. Metab. 2002;77:319–325. doi: 10.1016/S1096-7192(02)00195-6. PubMed DOI

D’Adamo P., Fassone L., Gedeon A., Janssen E.A., Bione S., Bolhuis P.A., Barth P.G., Wilson M., Haan E., Örstavik K.H., et al. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. Am. J. Hum. Genet. 1997;61:862–867. doi: 10.1086/514886. PubMed DOI PMC

Hijikata A., Yura K., Ohara O., Go M. Structural and functional analyses of Barth syndrome-causing mutations and alternative splicing in the tafazzin acyltransferase domain. Meta Gene. 2015;4:92–106. doi: 10.1016/j.mgene.2015.04.001. PubMed DOI PMC

Barth P.G., Scholte H.R., Berden J.A., Van der Klei-Van Moorsel J.M., Luyt-Houwen I.E.M., Veer-Korthof E.T.V.T., van der Harten J.J., Sobotka-Plojhar M.A. An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J. Neurol. Sci. 1983;62:327–355. doi: 10.1016/0022-510X(83)90209-5. PubMed DOI

Barth P.G., Wanders J.A.R., Vreken P. X-linked cardioskeletal myopathy and neutropenia (Barth syndrome)—MIM 302060. J. Pediatr. 1999;135:273–276. doi: 10.1016/S0022-3476(99)70118-6. PubMed DOI

Valianpour F., Wanders R.J.A., Overmars H., Vreken P., Van Gennip A.H., Baas F., Plecko B., Santer R., Becker K., Barth P.G. Cardiolipin deficiency in X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060): A study in cultured skin fibroblasts. J. Pediatr. 2002;141:729–733. doi: 10.1067/mpd.2002.129174. PubMed DOI

Schlame M., Towbin J.A., Heerdt P.M., Jehle R., DiMauro S., Blanck T.J.J. Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome. Ann. Neurol. 2002;51:634–637. doi: 10.1002/ana.10176. PubMed DOI

Schlame M., Kelley R.I., Feigenbaum A., Towbin J.A., Heerdt P.M., Schieble T., Wanders R.J.A., Di Mauro S., Blanck T.J.J. Phospholipid abnormalities in children with Barth syndrome. J. Am. Coll. Cardiol. 2003;42:1994–1999. doi: 10.1016/j.jacc.2003.06.015. PubMed DOI

Dudek J., Hartmann M., Rehling P. The role of mitochondrial cardiolipin in heart function and its implication in cardiac disease. Biochim. Biophys. Acta Mol. Basis Dis. 2019;1865:810–821. doi: 10.1016/j.bbadis.2018.08.025. PubMed DOI

Chistiakov D.A., Shkurat T.P., Melnichenko A.A., Grechko A.V., Orekhov A.N. The role of mitochondrial dysfunction in cardiovascular disease: A brief review. Ann. Med. 2018;50:121–127. doi: 10.1080/07853890.2017.1417631. PubMed DOI

Holthuis J.C., Menon A.K. Lipid landscapes and pipelines in membrane homeostasis. Nature. 2014;510:48–57. doi: 10.1038/nature13474. PubMed DOI

Horvath S.E., Daum G. Lipids of mitochondria. Prog. Lipid Res. 2013;52:590–614. doi: 10.1016/j.plipres.2013.07.002. PubMed DOI

Zinser E., Sperka-Gottlieb C.D., Fasch E.V., Kohlwein S.D., Paltauf F., Daum G. Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae. J. Bacteriol. 1991;173:2026–2034. doi: 10.1128/jb.173.6.2026-2034.1991. PubMed DOI PMC

Ball W.B., Neff J.K., Gohil V.M. The role of nonbilayer phospholipids in mitochondrial structure and function. FEBS Lett. 2017;592 doi: 10.1002/1873-3468.12887. PubMed DOI PMC

Nelson D.L., Cox M.M. Principles of Biochemistry. 6th ed. W. H. Freeman and Company; New York, NY, USA: 2013.

Böttinger L., Horvath S.E., Kleinschroth T., Hunte C., Daum G., Pfanner N., Becker T. Phosphatidylethanolamine and cardiolipin differentially dffect the stability of mitochondrial respiratory chain supercomplexes. J. Mol. Biol. 2012;423:677–686. doi: 10.1016/j.jmb.2012.09.001. PubMed DOI PMC

Cullis P.R., de Kruijff B. Lipid polymorphism and the functional roles of lipids in biological membranes. Biochim. Biophys. Acta. 1979;559:399–420. doi: 10.1016/0304-4157(79)90012-1. PubMed DOI

de Kruijff B., Cullis P.R., Verkleij A.J., Hope M.J., Van Echteld C.J.A., Taraschi T.F., Van Hoogevest P., Killian J.A., Rietveld A., Van der Steen A.T.M. Modulation of Lipid Polymorphism by Lipid Protein Interactions. In: Watts A., De Pont J.J.H.H.M., editors. Progress in Protein-Lipid Interactions. Elsevier; Amsterdam, The Netherlands: 1985. pp. 89–142.

de Kruijff B. Lipids beyond the bilayer. Nature. 1997;386:129–130. doi: 10.1038/386129a0. PubMed DOI

Garab G., Lohner K., Laggner P., Farkas T. Self-regulation of the lipid content of membranes by non-bilayer lipids: A hypothesis. Trends Plant Sci. 2000;5:489–494. doi: 10.1016/S1360-1385(00)01767-2. PubMed DOI

Rietveld A., van Kemenade T.J.J.M., Hak T., Verkleij A.J., De Kruijff B. The effect of cytochrome c oxidase on lipid polymorphism of model membranes containing cardiolipin. Eur. J. Biochem. 1987;164:137–140. doi: 10.1111/j.1432-1033.1987.tb11004.x. PubMed DOI

Simidjiev I., Stoylova S., Amenitsch H., Javorfi T., Mustardy L., Langgner P., Holzenburg A., Garab G. Self-assembly of large, ordered lamellae from non-bilayer lipids and integral membrane proteins in vitro. Proc. Natl. Acad. Sci. USA. 2000;97:1473–1476. doi: 10.1073/pnas.97.4.1473. PubMed DOI PMC

Seddon J.M., Templer R.H. Polymorphism of Lipid-Water Systems. In: Lipowsky R., Sackmann E., editors. Structure and Dynamics of Membranes, I. From Cells to Vesicles. North Holland; Amsterdam, The Netherlands: 1995. pp. 97–160.

Van Eerden F.J., de Jong D.H., de Vries A.H., Wassenaar T.A., Marrink S.J. Characterization of thylakoid lipid membranes from cyanobacteria and higher plants by molecular dynamics simulations. Biophys. Biochem. Acta Biomembr. 2015;1848:1319–1330. doi: 10.1016/j.bbamem.2015.02.025. PubMed DOI

Garab G., Ughy B., Goss R. Role of MGDG and non-bilayer lipid phases in the structure and dynamics of chloroplast thylakoid membranes. In: Nakamura Y., Li-Beisson Y., editors. Lipids in Plant and Algae Development, Subcellular Biochemistry. Springer International Publishing; Basel, Switzerland: 2016. pp. 127–157. PubMed

Garab G., Ughy B., de Waard P., Akhtar P., Javornik U., Kotakis C., Šket P., Karlický V., Materová Z., Špunda V., et al. Lipid polymorphism in chloroplast thylakoid membranes–as revealed by 31P-NMR and time-resolved merocyanine fluorescence spectroscopy. Sci. Rep. 2017;7:13343–13354. doi: 10.1038/s41598-017-13574-y. PubMed DOI PMC

Kotakis C., Akhtar P., Zsiros O., Garab G., Lambrev P.H. Increased thermal stability of photosystem II and the macro-organization of thylakoid membranes, induced by co-solutes, associated with changes in the lipid-phase behaviour of thylakoid membranes. Photosynthetica. 2018;56:254–264. doi: 10.1007/s11099-018-0782-z. DOI

Wilhelm C., Goss R., Garab G. The fluid-mosaic membrane theory in the context of photosynthetic membranes: Is the thylakoid membrane more like a mixed crystal or like a fluid? J. Plant Physiol. 2020;252:153246–153263. doi: 10.1016/j.jplph.2020.153246. PubMed DOI

Dlouhý O., Kurasová I., Karlický V., Javornik U., Šket P., Petrova N.Z., Krumova S.B., Plavec J., Ughy B., Špunda V., et al. Modulation of non-bilayer lipid phases and the structure and functions of thylakoid membranes: Effects on the water-soluble enzyme violaxanthin de-epoxidase. Sci. Rep. 2020;10:11959–11972. doi: 10.1038/s41598-020-68854-x. PubMed DOI PMC

Ughy B., Karlický V., Dlouhý O., Javornik U., Materova Z., Zsiros O., Šket P., Plavec J., Špunda V., Garab G. Lipid-polymorphism of plant thylakoid membranes. Enhanced non-bilayer lipid phases associated with increased membrane permeability. Physiol. Plant. 2019;166:278–287. doi: 10.1111/ppl.12929. PubMed DOI

Szeto H.H. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br. J. Pharm. 2014;171:2029–2050. doi: 10.1111/bph.12461. PubMed DOI PMC

Szeto H.H., Birk A.V. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin. Pharm. 2014;96:672–683. doi: 10.1038/clpt.2014.174. PubMed DOI PMC

Zhao K., Luo G., Zhao G.M., Schiller P.W., Szeto H.H. Transcellular transport of a highly polar 3+ net charge opioid tetrapeptide. J. Pharm. Exp. 2003;304:425–432. doi: 10.1124/jpet.102.040147. PubMed DOI

Reddy P.H., Manczak M., Kandimalla R. Mitochondria-targeted small molecule SS31: A potential candidate for the treatment of Alzheimer’s disease. Hum. Mol. Genet. 2017;26:1483–1496. doi: 10.1093/hmg/ddx052. PubMed DOI PMC

Birk A.V., Liu S., Soong Y., Mills W., Singh P., Warren J.D., Seshan S.V., Pardee J.D., Szeto H.H. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J. Am. Soc. Nephrol. 2013;24:1250–1261. doi: 10.1681/ASN.2012121216. PubMed DOI PMC

Birk A.V., Chao W.M., Liu S., Soong Y., Szeto H.H. Disruption of cytochrome c heme coordination is responsible for mitochondrial injury during ischemia. Biochim. Biophys. Acta. 2015;1847:1075–1084. doi: 10.1016/j.bbabio.2015.06.006. PubMed DOI PMC

Birk A.V., Chao W.M., Bracken C., Warren J.D., Szeto H.H. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br. J. Pharm. 2014;171:2017–2028. doi: 10.1111/bph.12468. PubMed DOI PMC

Gasanov S.E., Salakhutdinov B.A., Aripov T.F. Formation of nonbilayer structures in phospholipid membrane induced by cationic polypeptides. Biol. Membr. 1990;7:1045–1055.

Gasanov S.E., Kamaev F.G., Salakhutdinov B.A., Aripov T.F. The fusogenic properties of the cytotoxins of cobra venom in a model membrane system. Nauchnye Dokl. Vyss. Shkoly. Biol. Nauk. 1990;2:42–50. PubMed

Gasanov S.E., Shrivastava I.H., Israilov F.S., Kim A.A., Rylova K.A., Zhang B., Dagda R.K. Naja naja oxiana cobra venom cytotoxins CTI and CTII disrupt mitochondrial membrane integrity: Implications for basic three-fingered cytotoxins. PLoS ONE. 2015;10:e0129248. doi: 10.1371/journal.pone.0129248. PubMed DOI PMC

Gasanov S.E., Vernon L.P., Aripov T.F. Modification of phospholipid membrane structure by the plant toxic peptide Pyrularia thionin. Arch. Biochem. Biophys. 1993;301:367–374. doi: 10.1006/abbi.1993.1157. PubMed DOI

Zhang B., Li F., Chen Z., Shrivastava I.H., Gasanoff E.S., Dagda R.K. Naja mossambica mossambica cobra cardiotoxin targets mitochondria to disrupt mitochondrial membrane structure and function. Toxins. 2019;11:152. doi: 10.3390/toxins11030152. PubMed DOI PMC

Aripov T.F., Gasanov S.E., Salakhutdinov B.A., Sadykov A.S. Studies on the interaction of cobra venom cytotoxin with oriented phospholipid multilayers. Dokl. Akad. Nauk SSSR. 1986;288:728–730. PubMed

Gasanov S.E., Alsarraj M.A., Gasanov N.E., Rael E.D. Cobra venom cytotoxin free of phospholipase A2 and its effect on model membranes and T leukemia cells. J. Membr. Biol. 1997;155:133–142. doi: 10.1007/s002329900165. PubMed DOI

Aripov T.F., Gasanov S.E., Salakhutdinov B.A., Rozenshtein I.A., Kamaev F.G. Central Asian cobra venom cytotoxins-induced aggregation, permeability and fusion of liposomes. Gen. Physiol. Biophys. 1989;8:459–473. PubMed

Fox C.A., Ellison P., Ikon N., Ryan R.O. Calcium-induced transformation of cardiolipin nanodisks. Biochim. Biophys. Acta Biomembr. 2019;1861:1030–1036. doi: 10.1016/j.bbamem.2019.03.005. PubMed DOI PMC

De Kruijff B., Verkleij A.J., Leunissen-Bijvelt J., van Echteld C.J.A., Hille J., Rijnbout H. Further aspects of the Ca2+-dependent polymorphism of bovine heart cardiolipin. Biochim. Biophys. Acta. 1982;693:1–12. doi: 10.1016/0005-2736(82)90464-3. PubMed DOI

Gasanov S.E., Salakhutdinov B.A., Aripov T.F. Possible applications of deactivation of triplet-excited state and sensitized delayed fluorescence for studying liposome fusion. Biofizika. 1990;35:879–880.

Gasanov S.E., Aripov T.F., Salakhutdinov B.A. Intermembrane exchange of lipids induced by cobra venom cytotoxins. Biofizika. 1990;35:958–962. PubMed

Gasanov S.E., Aripov T.F., Gasanov E.E. Study on Structure of Phospholipid Membranes Modified by Membrane-Active Polypeptides. Nuclear Physics Institute of UzSSR Academy of Sciences; Tashkent, Uzbekistan: 1988.

Kondadi A.K., Anand R., Reichert A.S. Cristae membrane dynamics—A paradigm change. Trends Cell Biol. 2020;30:923–936. doi: 10.1016/j.tcb.2020.08.008. PubMed DOI

Chan D.C. Mitochondrial dynamics and its involvement in disease. Annu. Rev. Pathol. Mech. Dis. 2020;15:235–259. doi: 10.1146/annurev-pathmechdis-012419-032711. PubMed DOI

Colina-Tenorio L., Horten P., Pfanner N., Rampelt H. Shaping the mitochondrial inner membrane in health and disease. J. Intern. Med. 2020;287:645–664. doi: 10.1111/joim.13031. PubMed DOI

Kondadi A.K., Anand R., Hänsch S., Urbach J., Zobel T., Wolf D.M., Segawa M., Liesa M., Shirihai O.S., Weidtkamp-Peters S., et al. Cristae undergo continuous cycles of membrane remodelling in a MICOS-dependent manner. EMBO Rep. 2020;21:e49776. doi: 10.15252/embr.201949776. PubMed DOI PMC

Frey T.G., Mannella C.A. The internal structure of mitochondria. Trends Biochem. Sci. 2000;25:319–324. doi: 10.1016/S0968-0004(00)01609-1. PubMed DOI

Frey T.G., Renken C.W., Perkins G.A. Insight into mitochondrial structure and function from electron tomography. Biochim. Biophys. Acta. 2002;1555:196–203. doi: 10.1016/S0005-2728(02)00278-5. PubMed DOI

Liesa M. Why does a mitochondrion need its individual cristae to be functionally autonomous? Mol. Cell. Oncol. 2020;7:1705119. doi: 10.1080/23723556.2019.1705119. PubMed DOI PMC

Eramo M.J., Lisnyak V., Formosa L.E., Ryan M.T. The ‘mitochondrial contact site and cristae organising system’ (MICOS) in health and human disease. J. Biochem. 2020;167:243–255. doi: 10.1093/jb/mvz111. PubMed DOI

Khosravi S., Harner M.E. The MICOS complex, a structural element of mitochondria with versatile functions. Biol. Chem. 2020;401:765–778. doi: 10.1515/hsz-2020-0103. PubMed DOI

Stephan T., Brüser C., Deckers M., Steyer A.M., Balzarotti F., Barbot M. MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. EMBO J. 2020;39:e104105. doi: 10.15252/embj.2019104105. PubMed DOI PMC

Anand R., Kondadi A.K., Meisterknecht J., Golombek M., Nortmann O., Riedel J., Peifer-Weiß L., Brocke-Ahmadinejad N., Schlütermann D., Stork B., et al. MIC26 and MIC27 cooperate to regulate cardiolipin levels and the landscape of OXPHOS complexes. Life Sci. Alliance. 2020;3:e202000711. doi: 10.26508/lsa.202000711. PubMed DOI PMC

Itoh K., Nakamura K., Iijima M., Sesaki H. Mitochondrial dynamics in neurodegeneration. Trends Cell Biol. 2013;23:64–71. doi: 10.1016/j.tcb.2012.10.006. PubMed DOI PMC

Acehan D., Vaz F., Houtkooper R.H., James J., Moore V., Tokunaga C., Kulik W., Wansapura J., Toth M.J., Strauss A., et al. Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J. Biol. Chem. 2011;286:899–908. doi: 10.1074/jbc.M110.171439. PubMed DOI PMC

Clarke S.L., Bowron A., Gonzalez I.L., Groves S.J., Newbury-Ecob R., Clayton N., Martin R.P., Tsai-Goodman B., Garratt V., Ashworth M., et al. Barth syndrome. Orphanet J. Rare Dis. 2013;8:23. doi: 10.1186/1750-1172-8-23. PubMed DOI PMC

Gao S., Hu J. Mitochondrial Fusion: The machineries in and out. Trends Cell Biol. 2021;31:62–74. doi: 10.1016/j.tcb.2020.09.008. PubMed DOI

Schuster R., Anton V., Simões T., Altin S., den Brave F., Hermanns T., Hospenthal M., Komander D., Dittmar P.G., Dohmen P.J., et al. Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation. Life Sci. Alliance. 2020;3:e201900476. doi: 10.26508/lsa.201900476. PubMed DOI PMC

Ge Y., Shi X., Boopathy S., McDonald J., Smith A.W., Chao L.H. Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane. eLife. 2020;9:e50973. doi: 10.7554/eLife.50973. PubMed DOI PMC

Cullis P., De Kruijff B., Hope M., Nayar R., Rietveld A., Verkleij A. Structural properties of phospholipids in the rat liver inner mitochondrial membrane. A 31P-NMR study. Biochim. Biophys. Acta Biomembr. 1980;600:625–635. doi: 10.1016/0005-2736(80)90466-6. PubMed DOI

Segal N.K., Gasanov S.E., Palamarchuk L.A., Ius’kovich A.K., Kolesova G.M., Mansurova S.E., Yaguzhinsky L.S. Mitochondrial proteolipids. Biokhimiia. 1993;58:1812–1819. PubMed

Fillingame R.H. The proton-translocating pumps of oxidative phosphorylation. Annu. Rev. Biochem. 1980;49:1079–1113. doi: 10.1146/annurev.bi.49.070180.005243. PubMed DOI

Daum G. Lipids of mitochondria. Biochim. Biophys. Acta Biomembr. 1985;822:1–42. doi: 10.1016/0304-4157(85)90002-4. PubMed DOI

Stoldt S., Wenzel D., Kehrein K., Riedel D., Ott M., Jakobs S. Spatial orchestration of mitochondrial translation and OXPHOS complex assembly. Nat. Cell Biol. 2018;20:528–534. doi: 10.1038/s41556-018-0090-7. PubMed DOI

Krasinskaya I.P., Marshansky V.N., Dragunova S.F., Yaguzhinsky L.S. Relationships of respiratory chain and ATP-synthetase in energized mitochondria. FEBS Lett. 1984;167:176–180. doi: 10.1016/0014-5793(84)80856-X. PubMed DOI

Toth A., Meyrat A., Stoldt S., Santiago R., Wenzel D., Jakobs S., von Ballmoos C., Ott M. Kinetic coupling of the respiratory chain with ATP synthase, but not proton gradients, drives ATP production in cristae membranes. Proc. Natl. Acad. Sci. USA. 2020;117:2412–2421. doi: 10.1073/pnas.1917968117. PubMed DOI PMC

Weichselbaum E., Österbauer M., Knyazev D.G., Batishchev O.V., Akimov S.A., Nguyen T.H., Zhang C., Knör G., Agmon N., Carloni P., et al. Origin of proton affinity to membrane/water interfaces. Sci. Rep. 2017;7:4553. doi: 10.1038/s41598-017-04675-9. PubMed DOI PMC

Medvedev E.S., Stuchebrukhov A.A. Proton diffusion along biological membranes. J. Phys. Condens. Matter. 2011;23:234103. doi: 10.1088/0953-8984/23/23/234103. PubMed DOI

Yaguzhinsky L.S., Boguslavsky L.I., Volkov A.G., Rakhmaninova A.B. Synthesis of ATP coupled with action of membrane protonic pumps at the octane–water interface. Nature. 1976;259:494–496. doi: 10.1038/259494a0. PubMed DOI

Antonenko Y.N., Kovbasnjuk O.N., Yaguzhinsky L.S. Evidence in favor of the existence of a kinetic barrier for proton transfer from a surface of bilayer phospholipid membrane to bulk water. Biochim. Biophys. Acta Biomembr. 1993;1150:45–50. doi: 10.1016/0005-2736(93)90119-K. PubMed DOI

Evtodienko V.Y., Antonenko Y.N., Yaguzhinsky L.S. Increase of local hydrogen ion gradient near bilayer lipid membrane under the conditions of catalysis of proton transfer across the interface. FEBS Lett. 1998;425:222–224. doi: 10.1016/S0014-5793(98)00233-6. PubMed DOI

Nesterov S., Chesnokov Y., Kamyshinsky R., Panteleeva A., Lyamzaev K., Vasilov R., Yaguzhinsky L. Ordered clusters of the complete oxidative phosphorylation system in cardiac mitochondria. Int. J. Mol. Sci. 2021;22:1462. doi: 10.3390/ijms22031462. PubMed DOI PMC

Eroshenko L.V., Marakhovskaya A.S., Vangeli I.M., Semenyuk P.I., Orlov V.N., Yaguzhinsky L.S. Bronsted acids Bounded to the mitochondrial membranes as a substrate for ATP synthase. Dokl. Biochem. Biophys. 2012;444:158–161. doi: 10.1134/S160767291203009X. PubMed DOI

Moiseeva V.S., Motovilov K.A., Lobysheva N.V., Orlov V.N., Yaguzhinsky L.S. The formation of metastable bond between protons and mitoplast surface. Dokl. Biochem. Biophys. 2011;438:127–130. doi: 10.1134/S1607672911030069. PubMed DOI

Ban T., Heymann J.A.W., Song J., Hinshaw J.E., Chan D.C. OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. Hum. Mol. Genet. 2010;19:2113–2122. doi: 10.1093/hmg/ddq088. PubMed DOI PMC

Liu R., Chan D.C. OPA1 and cardiolipin team up for mitochondrial fusion. Cell Biol. 2017;19:760–762. doi: 10.1038/ncb3565. PubMed DOI PMC

Kameoka S., Adachi Y., Okamoto K.M., Hiromi Sesaki H. Phosphatidic acid and cardiolipin coordinate mitochondrial dynamics. Trends Cell Biol. 2018;28:67–76. doi: 10.1016/j.tcb.2017.08.011. PubMed DOI PMC

Spikes T.E., Montgomery M.G., Walker J.E. Structure of the dimeric ATP synthase from bovine mitochondria. Proc. Natl. Acad. Sci. USA. 2020;117:23519–23526. doi: 10.1073/pnas.2013998117. PubMed DOI PMC

Guo H., Bueler S.A., Rubinstein J.L. Atomic model for the dimeric FO region of mitochondrial ATP synthase. Science. 2017;358:936–940. doi: 10.1126/science.aao4815. PubMed DOI PMC

Liu Y.P., Gasanoff E.S. Role of non-bilayer structures in mitochondrial membranes; Proceedings of the 7th European Joint Theoretical/Experimental Meeting on Membranes; Graz, Austria. 7–9 April 2021; p. 104.

Pettersen E.F., Goddard T.D., Huang C.C., Meng E.C., Couch G.S., Croll T.I., Morris J.H., Ferrin T.E. UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 2021;30:70–82. doi: 10.1002/pro.3943. PubMed DOI PMC

Goddard T.D., Huang C.C., Meng E.C., Pettersen E.F., Couch G.S., Morris J.H., Ferrin T.E. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 2018;27:14–25. doi: 10.1002/pro.3235. PubMed DOI PMC

Extracellular freezing induces a permeability transition in the inner membrane of muscle mitochondria of freeze-sensitive but not freeze-tolerant Chymomyza costata larvae

Editorial

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

Short-Chained Alcohols Make Membrane Surfaces Conducive for Melittin Action: Implication for the Physiological Role of Alcohols in Cells

Bee Venom Melittin Disintegrates the Respiration of Mitochondria in Healthy Cells and Lymphoblasts, and Induces the Formation of Non-Bilayer Structures in Model Inner Mitochondrial Membranes