Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
34864056
PubMed Central
PMC8728584
DOI
10.1016/j.jbc.2021.101462
PII: S0021-9258(21)01271-0
Knihovny.cz E-resources
- Keywords
- Barth syndrome, mitochondria, phosphatidylglycerol, tafazzin, valproic acid,
- MeSH
- Acyltransferases metabolism MeSH
- Barth Syndrome * metabolism MeSH
- Phenotype MeSH
- Phosphatidylglycerols * antagonists & inhibitors metabolism MeSH
- Cardiolipins * genetics metabolism MeSH
- Humans MeSH
- Saccharomyces cerevisiae metabolism MeSH
- Transcription Factors metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acyltransferases MeSH
- Phosphatidylglycerols * MeSH
- Cardiolipins * MeSH
- TAFAZZIN protein, human MeSH Browser
- Transcription Factors MeSH
Barth syndrome (BTHS) is an inherited mitochondrial disorder characterized by a decrease in total cardiolipin and the accumulation of its precursor monolysocardiolipin due to the loss of the transacylase enzyme tafazzin. However, the molecular basis of BTHS pathology is still not well understood. Here we characterize the double mutant pgc1Δtaz1Δ of Saccharomyces cerevisiae deficient in phosphatidylglycerol-specific phospholipase C and tafazzin as a new yeast model of BTHS. Unlike the taz1Δ mutant used to date, this model accumulates phosphatidylglycerol, thus better approximating the human BTHS cells. We demonstrate that increased phosphatidylglycerol in this strain leads to more pronounced mitochondrial respiratory defects and an increased incidence of aberrant mitochondria compared to the single taz1Δ mutant. We also show that the mitochondria of the pgc1Δtaz1Δ mutant exhibit a reduced rate of respiration due to decreased cytochrome c oxidase and ATP synthase activities. Finally, we determined that the mood-stabilizing anticonvulsant valproic acid has a positive effect on both lipid composition and mitochondrial function in these yeast BTHS models. Overall, our results show that the pgc1Δtaz1Δ mutant better mimics the cellular phenotype of BTHS patients than taz1Δ cells, both in terms of lipid composition and the degree of disruption of mitochondrial structure and function. This favors the new model for use in future studies.
See more in PubMed
Basu Ball W., Neff J.K., Gohil V.M. The role of nonbilayer phospholipids in mitochondrial structure and function. FEBS Lett. 2018;592:1273–1290. PubMed PMC
Dugail I., Kayser B.D., Lhomme M. Specific roles of phosphatidylglycerols in hosts and microbes. Biochimie. 2017;141:47–53. PubMed
Furse S. Is phosphatidylglycerol essential for terrestrial life? J. Chem. Biol. 2017;10:1–9. PubMed PMC
Sato N. Roles of the acidic lipids sulfoquinovosyl diacylglycerol and phosphatidylglycerol in photosynthesis: Their specificity and evolution. J. Plant Res. 2004;117:495–505. PubMed
Günther A., Ruppert C., Schmidt R., Markart P., Grimminger F., Walmrath D., Seeger W. Surfactant alteration and replacement in acute respiratory distress syndrome. Respir. Res. 2001;2:353–364. PubMed PMC
Voelker D.R., Numata M. Phospholipid regulation of innate immunity and respiratory viral infection. J. Biol. Chem. 2019;294:4282–4289. PubMed PMC
Jiang F., Ryan M.T., Schlame M., Zhao M., Gu Z., Klingenberg M., Pfanner N., Greenberg M.L. Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function. J. Biol. Chem. 2000;275:22387–22394. PubMed
Vaena de Avalos S., Su X., Zhang M., Okamoto Y., Dowhan W., Hannun Y.A. The phosphatidylglycerol/cardiolipin biosynthetic pathway is required for the activation of inositol phosphosphingolipid phospholipase C, Isc1p, during growth of Saccharomyces cerevisiae. J. Biol. Chem. 2005;280:7170–7177. PubMed
Baile M.G., Sathappa M., Lu Y.-W., Pryce E., Whited K., McCaffery J.M., Han X., Alder N.N., Claypool S.M. Unremodeled and remodeled cardiolipin are functionally indistinguishable in yeast. J. Biol. Chem. 2014;289:1768–1778. PubMed PMC
Chicco A.J., Sparagna G.C. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am. J. Physiol. Cell Physiol. 2007;292:C33–44. PubMed
Claypool S.M., Koehler C.M. The complexity of cardiolipin in health and disease. Trends Biochem. Sci. 2012;37:32–41. PubMed PMC
Vreken P., Valianpour F., Nijtmans L.G., Grivell L.A., Plecko B., Wanders R.J., Barth P.G. Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome. Biochem. Biophys. Res. Commun. 2000;279:378–382. PubMed
Gu Z., Valianpour F., Chen S., Vaz F.M., Hakkaart G.A., Wanders R.J.A., Greenberg M.L. Aberrant cardiolipin metabolism in the yeast taz1 mutant: A model for Barth syndrome. Mol. Microbiol. 2004;51:149–158. PubMed
Ma L., Vaz F.M., Gu Z., Wanders R.J.A., Greenberg M.L. The human TAZ gene complements mitochondrial dysfunction in the yeast taz1Delta mutant. Implications for Barth syndrome. J. Biol. Chem. 2004;279:44394–44399. PubMed
Simocková M., Holic R., Tahotná D., Patton-Vogt J., Griac P. Yeast Pgc1p (YPL206c) controls the amount of phosphatidylglycerol via a phospholipase C-type degradation mechanism. J. Biol. Chem. 2008;283:17107–17115. PubMed PMC
Pokorná L., Čermáková P., Horváth A., Baile M.G., Claypool S.M., Griač P., Malínský J., Balážová M. Specific degradation of phosphatidylglycerol is necessary for proper mitochondrial morphology and function. Biochim. Biophys. Acta. 2016;1857:34–45. PubMed PMC
Matsumura A., Higuchi J., Watanabe Y., Kato M., Aoki K., Akabane S., Endo T., Oka T. Inactivation of cardiolipin synthase triggers changes in mitochondrial morphology. FEBS Lett. 2018;592:209–218. PubMed
Kubalová D., Káňovičová P., Veselá P., Awadová T., Džugasová V., Daum G., Malínský J., Balážová M. The lipid droplet protein Pgc1 controls the subcellular distribution of phosphatidylglycerol. FEMS Yeast Res. 2019;19 PubMed
Yu W., Daniel J., Mehta D., Maddipati K.R., Greenberg M.L. MCK1 is a novel regulator of myo-inositol phosphate synthase (MIPS) that is required for inhibition of inositol synthesis by the mood stabilizer valproate. PLoS One. 2017;12 PubMed PMC
Ju S., Greenberg M.L. Valproate disrupts regulation of inositol responsive genes and alters regulation of phospholipid biosynthesis. Mol. Microbiol. 2003;49:1595–1603. PubMed
Lu Y.-W., Galbraith L., Herndon J.D., Lu Y.-L., Pras-Raves M., Vervaart M., Van Kampen A., Luyf A., Koehler C.M., McCaffery J.M., Gottlieb E., Vaz F.M., Claypool S.M. Defining functional classes of Barth syndrome mutation in humans. Hum. Mol. Genet. 2016;25:1754–1770. PubMed PMC
Zhong Q., Greenberg M.L. Regulation of phosphatidylglycerophosphate synthase by inositol in Saccharomyces cerevisiae is not at the level of PGS1 mRNA abundance. J. Biol. Chem. 2003;278:33978–33984. PubMed
He Q., Greenberg M.L. Post-translational regulation of phosphatidylglycerolphosphate synthase in response to inositol. Mol. Microbiol. 2004;53:1243–1249. PubMed
Spencer C.T., Bryant R.M., Day J., Gonzalez I.L., Colan S.D., Thompson W.R., Berthy J., Redfearn S.P., Byrne B.J. Cardiac and clinical phenotype in Barth syndrome. Pediatrics. 2006;118:e337–e346. PubMed
Hauff K.D., Hatch G.M. Reduction in cholesterol synthesis in response to serum starvation in lymphoblasts of a patient with Barth syndrome. Biochem. Cell Biol. 2010;88:595–602. PubMed
Xu Y., Sutachan J.J., Plesken H., Kelley R.I., Schlame M. Characterization of lymphoblast mitochondria from patients with Barth syndrome. Lab. Invest. 2005;85:823–830. PubMed
Clarke S.L.N., Bowron A., Gonzalez I.L., Groves S.J., Newbury-Ecob R., Clayton N., Martin R.P., Tsai-Goodman B., Garratt V., Ashworth M., Bowen V.M., McCurdy K.R., Damin M.K., Spencer C.T., Toth M.J., et al. Barth syndrome. Orphanet J. Rare Dis. 2013;8:23. PubMed PMC
Gonzalvez F., D’Aurelio M., Boutant M., Moustapha A., Puech J.-P., Landes T., Arnauné-Pelloquin L., Vial G., Taleux N., Slomianny C., Wanders R.J., Houtkooper R.H., Bellenguer P., Møller I.M., Gottlieb E., et al. Barth syndrome: Cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. Biochim. Biophys. Acta. 2013;1832:1194–1206. PubMed
Schlame M. Cardiolipin remodeling and the function of tafazzin. Biochim. Biophys. Acta. 2013;1831:582–588. PubMed
Claypool S.M., Boontheung P., McCaffery J.M., Loo J.A., Koehler C.M. The cardiolipin transacylase, tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome. Mol. Biol. Cell. 2008;19:5143–5155. PubMed PMC
Zhong Q., Gohil V.M., Ma L., Greenberg M.L. Absence of cardiolipin results in temperature sensitivity, respiratory defects, and mitochondrial DNA instability independent of pet56. J. Biol. Chem. 2004;279:32294–32300. PubMed
Zhang M., Su X., Mileykovskaya E., Amoscato A.A., Dowhan W. Cardiolipin is not required to maintain mitochondrial DNA stability or cell viability for Saccharomyces cerevisiae grown at elevated temperatures. J. Biol. Chem. 2003;278:35204–35210. PubMed
O’Donnell T., Rotzinger S., Nakashima T.T., Hanstock C.C., Ulrich M., Silverstone P.H. Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain. Brain Res. 2000;880:84–91. PubMed
Vaden D.L., Ding D., Peterson B., Greenberg M.L. Lithium and valproate decrease inositol mass and increase expression of the yeast INO1 and INO2 genes for inositol biosynthesis. J. Biol. Chem. 2001;276:15466–15471. PubMed
Joshi A.S., Thompson M.N., Fei N., Hüttemann M., Greenberg M.L. Cardiolipin and mitochondrial phosphatidylethanolamine have overlapping functions in mitochondrial fusion in Saccharomyces cerevisiae. J. Biol. Chem. 2012;287:17589–17597. PubMed PMC
Gohil V.M., Thompson M.N., Greenberg M.L. Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine and cardiolipin biosynthetic pathways in Saccharomyces cerevisiae. J. Biol. Chem. 2005;280:35410–35416. PubMed
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. PubMed
Bui T.T., Suga K., Umakoshi H. Ergosterol-induced ordered phase in ternary lipid mixture systems of unsaturated and saturated phospholipid membranes. J. Phys. Chem. B. 2019;123:6161–6168. PubMed
Barth P.G., Scholte H.R., Berden J.A., Van der Klei-Van Moorsel J.M., Luyt-Houwen I.E., Van't Veer-Korthof E.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. PubMed
Kelley R.I., Cheatham J.P., Clark B.J., Nigro M.A., Powell B.R., Sherwood G.W., Sladky J.T., Swisher W.P. X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria. J. Pediatr. 1991;119:738–747. PubMed
Takeda A., Sudo A., Yamada M., Yamazawa H., Izumi G., Nishino I., Ariga T. Barth syndrome diagnosed in the subclinical stage of heart failure based on the presence of lipid storage myopathy and isolated noncompaction of the ventricular myocardium. Eur. J. Pediatr. 2011;170:1481–1484. PubMed
Acehan D., Xu Y., Stokes D.L., Schlame M. Comparison of lymphoblast mitochondria from normal subjects and patients with Barth syndrome using electron microscopic tomography. Lab. Invest. 2007;87:40–48. PubMed PMC
Mannella C.A. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim. Biophys. Acta. 2006;1763:542–548. PubMed
de Taffin de Tilques M., Tribouillard-Tanvier D., Tétaud E., Testet E., di Rago J.-P., Lasserre J.-P. Overexpression of mitochondrial oxodicarboxylate carrier (ODC1) preserves oxidative phosphorylation in a yeast model of Barth syndrome. Dis. Model. Mech. 2017;10:439–450. PubMed PMC
Paumard P., Vaillier J., Coulary B., Schaeffer J., Soubannier V., Mueller D.M., Brèthes D., di Rago J.-P., Velours J. The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J. 2002;21:221–230. PubMed PMC
Ouellet D., Bramson C., Roman D., Remmers A., Randinitis E., Milton A., Gardner M. Effects of three cytochrome P450 inhibitors, ketoconazole, fluconazole, and paroxetine, on the pharmacokinetics of lasofoxifene. Br. J. Clin. Pharmacol. 2007;63:59–66. PubMed PMC
Feng L., Wan Z., Wang X., Li R., Liu W. Relationship between antifungal resistance of fluconazole resistant Candida albicans and mutations in ERG11 gene. Chin. Med. J. (Engl.) 2010;123:544–548. PubMed
Niwa T., Imagawa Y., Yamazaki H. Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr. Drug Metab. 2014;15:651–679. PubMed
Wen X., Wang J.-S., Kivistö K.T., Neuvonen P.J., Backman J.T. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: Preferential inhibition of cytochrome P450 2C9 (CYP2C9) Br. J. Clin. Pharmacol. 2001;52:547–553. PubMed PMC
Gunes A., Bilir E., Zengil H., Babaoglu M.O., Bozkurt A., Yasar U. Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy patients. Basic Clin. Pharmacol. Toxicol. 2007;100:383–386. PubMed
Loper J.C. Cytochrome P450 lanosterol 14α-demethylase (CYP51): Insights from molecular genetic analysis of the ERG11 gene in Saccharomyces cerevisiae. J. Steroid Biochem. Mol. Biol. 1992;43:1107–1116. PubMed
Chaillot J., Tebbji F., García C., Wurtele H., Pelletier R., Sellam A. pH-dependant antifungal activity of valproic acid against the human fungal pathogen Candida albicans. Front. Microbiol. 2017;8:1956. PubMed PMC
Garaiová M., Zambojová V., Simová Z., Griač P., Hapala I. Squalene epoxidase as a target for manipulation of squalene levels in the yeast Saccharomyces cerevisiae. FEMS Yeast Res. 2014;14:310–323. PubMed
Griac P., Swede M.J., Henry S.A. The role of phosphatidylcholine biosynthesis in the regulation of the INO1 gene of yeast. J. Biol. Chem. 1996;271:25692–25698. PubMed
Voth W.P., Jiang Y.W., Stillman D.J. New ‘marker swap’ plasmids for converting selectable markers on budding yeast gene disruptions and plasmids. Yeast. 2003;20:985–993. PubMed
Gietz R.D., Woods R.A. Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol. 2002;350:87–96. PubMed
Strádalová V., Stahlschmidt W., Grossmann G., Blazíková M., Rachel R., Tanner W., Malinsky J. Furrow-like invaginations of the yeast plasma membrane correspond to membrane compartment of Can1. J. Cell Sci. 2009;122:2887–2894. PubMed
Carman G.M., Belunis C.J. Phosphatidylglycerophosphate synthase activity in Saccharomyces cerevisiae. Can. J. Microbiol. 1983;29:1452–1457. PubMed
Valachovič M., Hapala I. In: Vaccine Adjuvants: Methods and Protocols. Fox C.B., editor. Springer; New York, NY: 2017. Biosynthetic approaches to squalene production: The case of yeast; pp. 95–106. Methods in Molecular Biology. PubMed
Šimová Z., Poloncová K., Tahotná D., Holič R., Hapala I., Smith A.R., White T.C., Griač P. The yeast Saccharomyces cerevisiae Pdr16p restricts changes in ergosterol biosynthesis caused by the presence of azole antifungals. Yeast. 2013;30:229–241. PubMed
Holič R., Šimová Z., Ashlin T., Pevala V., Poloncová K., Tahotná D., Kutejová E., Cockcroft S., Griač P. Phosphatidylinositol binding of Saccharomyces cerevisiae Pdr16p represents an essential feature of this lipid transfer protein to provide protection against azole antifungals. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2014;1841:1483–1490. PubMed PMC
Two Different Phospholipases C, Isc1 and Pgc1, Cooperate To Regulate Mitochondrial Function