|Alencar MB, Ramos EV, Silber AM, Zíková A, Oliveira MF (2022) The extraordinary energy metabolism of the bloodstream Trypanosoma brucei forms: a critical review and a hypothesis. https://doi.org/10.26124/mitofit:2022-0009.v2 — 2022-12-05 published in Bioenerg Commun 2022.17.
» MitoFit Preprints 2022.09.v2.
Oliveira 2022 Abstract Bioblast: 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) exhibit unique metabolic features including: i) reduced expression and activity of mitochondrial enzymes; ii) respiration mediated by the glycerol phosphate shuttle (GPSh) and the Trypanosome alternative oxidase (TAO) that is intrinsically uncoupled from generation of mitochondrial membrane potential; 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 oxidants. Here, we critically review the main metabolic features of BSF and provide a hypothesis to explain the unusual metabolic network and its biological significance for this parasite form. We postulate that intrinsically uncoupled respiration provided by GPSh-TAO system would act as a preventive antioxidant defense by limiting mitochondrial superoxide production and complementing the NADPH-dependent scavenging antioxidant defenses to maintain parasite redox balance. Given the uncoupled nature of the GPSh-TAO system, BSF would avoid programmed cell death processes by maintaining mitochondrial membrane potential through the reversal of ATP synthase activity using the ATP generated by glycolysis. This unique “metabolic design” in BSF has no biological parallel outside of Trypanosomatids and highlights the enormous diversity of the parasite mitochondrial processes 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
AOX, Trypanosoma brucei, glycerophosphate shuttle, Bioblast 2022