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Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms
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SYSNO ASEP 0554949 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms Author(s) Serricchio, M. (CH)
Hierro Yap, Carolina (BC-A)
Schädeli, D. (CH)
Ben Hamidane, H. (QA)
Hemphill, A. (CH)
Graumann, J. (DE)
Zíková, Alena (BC-A) RID, ORCID
Butikofer, P. (CH)Number of authors 8 Source Title FASEB Journal. - : Wiley - ISSN 0892-6638
Roč. 35, č. 2 (2021)Number of pages 16 s. Publication form Online - E Language eng - English Country US - United States Keywords adp/atp carrier protein ; escherichia-coli ; atp synthase ; heart-mitochondria ; barth-syndrome ; cytochrome-c ; cell-culture ; complex ; growth ; expression ; ATP synthase ; cardiolipin ; electron transport chain ; mitochondria ; protein complexes ; trypanosomes Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA18-17529S GA ČR - Czech Science Foundation (CSF) EF16_019/0000759 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BC-A - RVO:60077344 UT WOS 000590888700001 EID SCOPUS 85096656101 DOI 10.1096/fj.202001579RR Annotation The mitochondrial inner membrane glycerophospholipid cardiolipin (CL) associates with mitochondrial proteins to regulate their activities and facilitate protein complex and supercomplex formation. Loss of CL leads to destabilized respiratory complexes and mitochondrial dysfunction. The role of CL in an organism lacking a conventional electron transport chain (ETC) has not been elucidated. Trypanosoma brucei bloodstream forms use an unconventional ETC composed of glycerol-3-phosphate dehydrogenase and alternative oxidase (AOX), while the mitochondrial membrane potential (Delta psi m) is generated by the hydrolytic action of the FoF1-ATP synthase (aka FoF1-ATPase). We now report that the inducible depletion of cardiolipin synthase (TbCls) is essential for survival of T brucei bloodstream forms. Loss of CL caused a rapid drop in ATP levels and a decline in the Delta psi m. Unbiased proteomic analyses revealed a reduction in the levels of many mitochondrial proteins, most notably of FoF1-ATPase subunits and AOX, resulting in a strong decline of glycerol-3-phosphate-stimulated oxygen consumption. The changes in cellular respiration preceded the observed decrease in FoF1-ATPase stability, suggesting that the AOX-mediated ETC is the first pathway responding to the decline in CL. Select proteins and pathways involved in glucose and amino acid metabolism were upregulated to counteract the CL depletion-induced drop in cellular ATP. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2022 Electronic address https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202001579RR
Number of the records: 1