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

Serricchio, Mauro; Hierro-Yap, Carolina; Schädeli, David; Ben Hamidane, Hisham; Hemphill, Andrew; Graumann, Johannes; Zíková, Alena; Bütikofer, Peter (2021). Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms. FASEB journal, 35(2), e21176. Federation of American Societies for Experimental Biology 10.1096/fj.202001579RR

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Serricchio, Mauro; Schädeli, David Lukas; Hemphill, Andrew and Bütikofer, Peter

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

14 Jan 2021 09:16

Last Modified:

04 Feb 2021 01:35

Publisher DOI:

10.1096/fj.202001579RR

PubMed ID:

33184899

Uncontrolled Keywords:

ATP synthase cardiolipin electron transport chain mitochondria protein complexes trypanosomes

BORIS DOI:

10.7892/boris.150863

URI:

https://boris.unibe.ch/id/eprint/150863

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