Redesigned and reversed: architectural and functional oddities of the trypanosomal ATP synthase

Parasitology. 2021 Sep;148(10):1151-1160. doi: 10.1017/S0031182021000202. Epub 2021 Feb 8.


Mitochondrial F-type adenosine triphosphate (ATP) synthases are commonly introduced as highly conserved membrane-embedded rotary machines generating the majority of cellular ATP. This simplified view neglects recently revealed striking compositional diversity of the enzyme and the fact that in specific life stages of some parasites, the physiological role of the enzyme is to maintain the mitochondrial membrane potential at the expense of ATP rather than to produce ATP. In addition, mitochondrial ATP synthases contribute indirectly to the organelle's other functions because they belong to major determinants of submitochondrial morphology. Here, we review current knowledge about the trypanosomal ATP synthase composition and architecture in the context of recent advances in the structural characterization of counterpart enzymes from several eukaryotic supergroups. We also discuss the physiological function of mitochondrial ATP synthases in three trypanosomatid parasites, Trypanosoma cruzi, Trypanosoma brucei and Leishmania, with a focus on their disease-causing life cycle stages. We highlight the reversed proton-pumping role of the ATP synthase in the T. brucei bloodstream form, the enzyme's potential link to the regulation of parasite's glycolysis and its role in generating mitochondrial membrane potential in the absence of mitochondrial DNA.

Keywords: ATP synthase; cryo-EM; mitochondria; mitochondrial membrane potential; oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Engineering*
  • Leishmania / enzymology*
  • Membrane Potential, Mitochondrial
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism
  • Trypanosoma brucei brucei / enzymology*
  • Trypanosoma cruzi / enzymology*


  • Protozoan Proteins
  • Mitochondrial Proton-Translocating ATPases