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

Carolina Hierro-Yap,Alena Zíková,Ondřej Gahura

doi:10.1017/s0031182021000202

Abstract

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.

Highlights

F-type adenosine triphosphate (ATP) synthases are bidirectional turbine-like enzymes coupling ATP synthesis or hydrolysis with proton translocation through biological membranes in bacteria and their endosymbiotic descendants, mitochondria and chloroplasts
Mitochondrial ATP synthases in most aerobic eukaryotes function as a major source of cellular ATP and the reversal of their activity is a manifestation of pathophysiological conditions (Campanella et al, 2009)
We summarize our knowledge of the ATP synthase importance for the disease-causing forms of medically relevant trypanosomatid parasites

Summary

Introduction

F-type adenosine triphosphate (ATP) synthases ( called F-ATPases of F1F0-ATPases) are bidirectional turbine-like enzymes coupling ATP synthesis or hydrolysis with proton translocation through biological membranes in bacteria and their endosymbiotic descendants, mitochondria and chloroplasts (for recent reviews see Junge and Nelson, 2015; Walker, 2017; Kuhlbrandt, 2019). They act as ATP-consuming proton pumps contributing to the generation of electrochemical membrane potential. Bacteria employ both modes depending on the species and growth conditions (Cotter and Hill, 2003). Its role switches during the parasite’s life cycle, from being an ATP producer in the insect form to an ATP consumer maintaining the vital mitochondrial membrane potential in the mammalian bloodstream form (BSF). This switch is associated with major rearrangement of mitochondrial morphology, possibly involving altered ATP synthase oligomerization. We summarize our knowledge of the ATP synthase importance for the disease-causing forms of medically relevant trypanosomatid parasites

Unexpected diversity of mitochondrial ATP synthases

Unique structural features of ATP synthases in Trypanosomatida

Findings

Role of the ATP synthase in trypanosomatid parasites