Alencar 2022 MitoFit

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Alencar 2022 MitoFit

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Alencar MB, Ramos EV, Silber AM, Oliveira MF (2022) A unifying hypothesis for the extraordinary energy metabolism of bloodstream Trypanosoma brucei. MitoFit Preprints 2022.9.


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A unifying hypothesis for the extraordinary energy metabolism of bloodstream Trypanosoma brucei

Alencar Mayke Bezerra, Ramos Emily V, Silber Ariel M, Oliveira Marcus F (2022-04-07) MitoFit Prep

Abstract: The parasite Trypanosoma brucei is the causative agent of sleeping sickness and involves an insect vector and a mammalian host through its complex life-cycle. T. brucei mammalian bloodstream forms (BSF) have unique metabolic features including: i) reduced expression and activity of mitochondrial enzymes; ii) intrinsically uncoupled respiration mediated by the glycerol phosphate shuttle (GPSh) and the Trypanosome alternative oxidase (TAO); iii) maintenance of mitochondrial membrane potential by ATP hydrolysis through the reversal of F1Fo ATP synthase activity; iv) strong reliance on glycolysis to meet their energy demands; v) high susceptibility to a variety of oxidants. Here, we provide a unifying hypothesis for this unusual metabolic network and its biological significance for BSF. We postulate that strong reliance on glycolysis would minimize the use of glucose by the pentose phosphate pathway that generates NADPH to maintain reduced thiols and scavenging antioxidant defenses. To this end, intrinsically uncoupled respiration provided by GPSh-TAO system would act as the main antioxidant defense by preventing mitochondrial superoxide production. This would reduce parasite investment in maintaining NADPH-dependent reduced thiols, sparing glucose to generate ATP by glycolysis. On the other hand, mitophagy and apoptosis-like processes would be limited by the maintenance of mitochondrial membrane potential through the reversal of ATP synthase activity. This unique “metabolic design” in BSF has no biological parallel and highlights the enormous diversity of mitochondrial processes present in trypanosomatids to adapt to distinct environments.

Keywords: Alternative oxidase; glycerol phosphate; reactive oxygen species; cell death; Trypanosoma brucei; mitophagy; antioxidant Bioblast editor: Tindle-Solomon L O2k-Network Lab: BR Sao Paulo Silber AM, BR Rio de Janeiro Oliveira MF

ORCID: ORCID.png Alencar MB, ORCID.png Silber Ariel M, ORCID.png Oliveira Marcus F


Organism: Protists 

Pathway: Gp 

AOX, Trypanosoma brucei, glycerophosphate shuttle, Bioblast 2022