Oliveira 2022 Abstract Bioblast

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Oliveira Marcus F
Alencar MB, Ramos EV, Silber AM, Zikova A, Oliveira Marcus F (2022) The extraordinary energy metabolism of the bloodstream Trypanosoma brucei forms: a critical review and a hypothesis. Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001
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Link: Bioblast 2022: BEC Inaugural Conference

Alencar Mayke Bezerra, Ramos Emily V, Silber Ariel M, Zikova Alena, Oliveira Marcus F (2022)

Event: Bioblast 2022

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: (1) reduced expression and activity of mitochondrial enzymes; (2) respiration mediated by the glycerol phosphate shuttle (GPSh) and the Trypanosome alternative oxidase (AOX) that is intrinsically uncoupled from generation of mitochondrial membrane potential; (3) maintenance of mitochondrial membrane potential by ATP hydrolysis through the reversal of F1FO ATP synthase activity; (4) strong reliance on glycolysis to meet their energy demands; (5) 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 apoptosis-like 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 parasites mitochondrial processes to adapt to distinct environments.

Keywords: Alternative oxidase; glycerol phosphate; reactive oxygen species; cell death; Trypanosoma brucei; mitophagy; antioxidant

O2k-Network Lab: BR Sao Paulo Silber AM, BR Rio de Janeiro Oliveira MF


Affiliations

Alencar MB1, Ramos EV1, Silber AM1, Zíková A2,3, Oliveira MF4,5
  1. Laboratory of Biochemistry of Trypanosomatids - LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
  2. Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branišovská 31, 37005, České Budějovice, Czech Republic
  3. Faculty of Science, University of South Bohemia, Branišovská 31, 37005, České Budějovice, Czech Republic
  4. Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
  5. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil - maroli@bioqmed.ufrj.br

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