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 (ΔΨm) is generated by the hydrolytic action of the Fo F1 -ATP synthase (aka Fo F1 -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 ΔΨm. Unbiased proteomic analyses revealed a reduction in the levels of many mitochondrial proteins, most notably of Fo F1 -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 Fo F1 -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.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• elektronový transportní řetězec metabolismus   MeSH
• energetický metabolismus genetika   MeSH
• geneticky modifikované organismy MeSH
• genový knockout * MeSH
• glycerolfosfátdehydrogenasa metabolismus   MeSH
• kardiolipiny genetika   metabolismus   MeSH
• membránové proteiny genetika   metabolismus   MeSH
• membránový potenciál mitochondrií genetika   MeSH
• mitochondriální membrány metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• oxidoreduktasy metabolismus   MeSH
• proteom MeSH
• proteomika MeSH
• protozoální proteiny genetika   metabolismus   MeSH
• rostlinné proteiny metabolismus   MeSH
• spotřeba kyslíku genetika   MeSH
• transferasy pro jiné substituované fosfátové skupiny genetika   metabolismus   MeSH
• Trypanosoma brucei brucei klasifikace   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH
• alternative oxidase MeSH Prohlížeč
• cardiolipin synthetase MeSH Prohlížeč
• elektronový transportní řetězec MeSH
• glycerolfosfátdehydrogenasa MeSH
• kardiolipiny MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• oxidoreduktasy MeSH
• proteom MeSH
• protozoální proteiny MeSH
• rostlinné proteiny MeSH
• transferasy pro jiné substituované fosfátové skupiny MeSH