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ATPaseTb2, a Unique Membrane-bound FoF1-ATPase Component, Is Essential in Bloodstream and Dyskinetoplastic Trypanosomes


The presence of the FoF1-ATP synthase in every aerobic organism suggests that evolution has settled on a basic blueprint for the complex rotary motor capable of synthesizing life’s universal energy currency—ATP. However, compared to yeast and mammalian models of the FoF1-ATP synthase, several recent studies have reported unique structural and functional features of this complex from organisms representing the clades of Chromalveolata, Archaeplastida and Excavata. One of the most striking cases is observed in trypanosomes, important parasites of humans and animals. Notably, the FoF1-ATP synthase/ATPase switches from synthesizing ATP in the insect vector life stage to hydrolyzing ATP in their mammalian hosts to generate the essential mitochondrial membrane potential (Δψm). Moreover, this indispensable FoF1-ATPase contains up to 14 trypanosome-specific subunits. Here we characterize one such novel subunit, ATPaseTb2. We demonstrate that this subunit is crucial for the survival of the infectious stage of trypanosomes, part of the fully assembled FoF1-complex and it is essential for maintaining the Δψm. Given the enzyme’s irreplaceable function and extraordinary composition, we believe that the FoF1-ATPase is an attractive drug target.


Vyšlo v časopise: ATPaseTb2, a Unique Membrane-bound FoF1-ATPase Component, Is Essential in Bloodstream and Dyskinetoplastic Trypanosomes. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004660
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004660

Souhrn

The presence of the FoF1-ATP synthase in every aerobic organism suggests that evolution has settled on a basic blueprint for the complex rotary motor capable of synthesizing life’s universal energy currency—ATP. However, compared to yeast and mammalian models of the FoF1-ATP synthase, several recent studies have reported unique structural and functional features of this complex from organisms representing the clades of Chromalveolata, Archaeplastida and Excavata. One of the most striking cases is observed in trypanosomes, important parasites of humans and animals. Notably, the FoF1-ATP synthase/ATPase switches from synthesizing ATP in the insect vector life stage to hydrolyzing ATP in their mammalian hosts to generate the essential mitochondrial membrane potential (Δψm). Moreover, this indispensable FoF1-ATPase contains up to 14 trypanosome-specific subunits. Here we characterize one such novel subunit, ATPaseTb2. We demonstrate that this subunit is crucial for the survival of the infectious stage of trypanosomes, part of the fully assembled FoF1-complex and it is essential for maintaining the Δψm. Given the enzyme’s irreplaceable function and extraordinary composition, we believe that the FoF1-ATPase is an attractive drug target.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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