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Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms
Author(s) -
Serricchio Mauro,
Hierro-Yap Carolina,
Schädeli David,
Ben Hamidane Hisham,
Hemphill Andrew,
Graumann Johannes,
Zíková Alena,
Bütikofer Peter
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001579rr
Subject(s) - trypanosoma brucei , cardiolipin , energy metabolism , metabolism , chemistry , biology , microbiology and biotechnology , biochemistry , endocrinology , phospholipid , membrane , gene
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 F o F 1 ‐ATP synthase (aka F o F 1 ‐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 F o F 1 ‐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 F o F 1 ‐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.