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

Carolina Hierro Yap, Karolina Subrtova, Ondřej Gahura, Brian Panicucci, Caroline Dewar, Christos Chinopoulos, Achim Schnaufer, Alena Zíková

Research output: Contribution to journalArticlepeer-review

Abstract

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, PCF), the FoF1-ATP synthase generates ATP by oxidative phosphorylation, while in the mammalian bloodstream form (BSF)this complex hydrolyzes ATP and maintains mitochondrial membrane potential (ΔΨm). 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 PCF cells, Tb1 silencing resulted in a decrease of FoF1-ATP synthase monomers and dimers, rerouting of mitochondrial electron transfer to the alternative oxidase(AOX), reduced growth rate and cellular ATP levels, and in elevated ΔΨm and total cellular reactive oxygen species levels. In BSF parasites, RNAi silencing of Tb1 by ~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 OSCP, a conserved subunit in T. brucei FoF1-ATP synthase. However, as expected, nearly complete Tb1 and OSCP suppression were lethal due to the inability to sustain ΔΨm. The diminishment of FoF1-ATPase complexes was further accompanied by a decreased ADP/ATP ratio and reduced oxygen consumption via AOX. Our data illuminate the often diametrically opposed bioenergetic consequences of FoF1-ATP synthase loss in insect versus mammalian forms of the parasite.
Original languageEnglish
Article number100357
Number of pages17
JournalJournal of Biological Chemistry
Volume296
Early online date1 Jan 2021
DOIs
Publication statusE-pub ahead of print - 1 Jan 2021

Keywords

  • trypanosoma brucei
  • bioenergetics
  • mitochondria
  • electron transport
  • ATP synthase
  • oxidative phosphorylation
  • ATPase
  • alternative oxidase
  • respiration
  • mitochondrial membrane potential

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