Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms

0554949 - BC 2022 RIV US eng J - Journal Article
Serricchio, M. - Hierro Yap, Carolina - Schädeli, D. - Ben Hamidane, H. - Hemphill, A. - Graumann, J. - Zíková, Alena - Butikofer, P.
Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms.
FASEB Journal. Roč. 35, č. 2 (2021). ISSN 0892-6638. E-ISSN 1530-6860
R&D Projects: GA ČR(CZ) GA18-17529S; GA MŠMT(CZ) EF16_019/0000759
Institutional support: RVO:60077344
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
OECD category: Biochemistry and molecular biology
Impact factor: 5.834, year: 2021
Method of publishing: Open access
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202001579RR

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.
Permanent Link: http://hdl.handle.net/11104/0329560