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Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype

. 2022 Jan ; 298 (1) : 101462. [epub] 20211202

Language English Country United States Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

Links

PubMed 34864056
PubMed Central PMC8728584
DOI 10.1016/j.jbc.2021.101462
PII: S0021-9258(21)01271-0
Knihovny.cz E-resources

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.

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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

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