Bioenergetic consequences of FoF1-ATP synthase/ATPase deficiency in two life cycle stages of Trypanosoma brucei

0553918 - BC 2022 RIV US eng J - Journal Article
Hierro Yap, Carolina - Šubrtová, Karolína - Gahura, Ondřej - Panicucci, Brian - Dewar, C. - Chinopoulos, C. - Schnaufer, A. - Zíková, Alena
Bioenergetic consequences of FoF1-ATP synthase/ATPase deficiency in two life cycle stages of Trypanosoma brucei.
Journal of Biological Chemistry. Roč. 296, JAN-JUN 2021 (2021), č. článku 100357. ISSN 0021-9258. E-ISSN 1083-351X
R&D Projects: GA MŠMT(CZ) EF16_019/0000759; GA ČR(CZ) GA18-17529S
Institutional support: RVO:60077344
Keywords : inducible expression system * blood-stream form * atp synthase * alternative oxidase * kinetoplast dna * energy-metabolism * glycolytic flux * protein * subunits * complex
OECD category: Biochemistry and molecular biology
Impact factor: 5.485, year: 2021
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0021925821001290?via%3Dihub

Mitochondrial ATP synthase is a reversible nanomotor synthesizing or hydrolyzing ATP depending on the potential across the membrane in which it is embedded. In the unicellular parasite Trypanosoma brucei, the direction of the complex depends on the life cycle stage of this digenetic parasite: in the midgut of the tsetse fly vector (procyclic form), the FoF1-ATP synthase generates ATP by oxidative phosphorylation, whereas in the mammalian bloodstream form, this complex hydrolyzes ATP and maintains mitochondrial membrane potential (Delta Psi m). The trypanosome FoF1-ATP synthase contains numerous lineage-specific subunits whose roles remain unknown. Here, we seek to elucidate the function of the lineage-specific protein Tb1, the largest membrane-bound subunit. In procyclic form cells, Tb1 silencing resulted in a decrease of FoF1-ATP synthase monomers and dimers, rerouting of mitochondrial electron transfer to the alternative oxidase, reduced growth rate and cellular ATP levels, and elevated Delta Psi m and total cellular reactive oxygen species levels. In bloodstream form parasites, RNAi silencing of Tb1 by similar to 90% resulted in decreased FoF1-ATPase monomers and dimers, but it had no apparent effect on growth. The same findings were obtained by silencing of the oligomycin sensitivity-conferring protein, a conserved subunit in T. brucei FoF1-ATP synthase. However, as expected, nearly complete Tb1 or oligomycin sensitivity-conferring protein suppression was lethal because of the inability to sustain Delta Psi m. The diminishment of FoF1-ATPase complexes was further accompanied by a decreased ADP/ATP ratio and reduced oxygen consumption via the alternative oxidase. Our data illuminate the often diametrically opposed bioenergetic consequences of FoF1-ATP synthase loss in insect versus mammalian forms of the parasite.
Permanent Link: http://hdl.handle.net/11104/0328599