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Alencar 2022 MitoFit

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

» MitoFit Preprints 2022.9.

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

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

Abstract: Version 2 (v2) 2022-07-07 doi:10.26124/mitofit:2022-0009.v2

Version 1 (v1) 2022-04-07 doi:10.26124/mitofit:2022-0009.v1 - »Link to all versions«

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

ORCID: Alencar MB, Silber Ariel M, Zikova Alena, Oliveira Marcus F

Labels:

Organism: Protists

Pathway: Gp

AOX, Trypanosoma brucei, glycerophosphate shuttle, Bioblast 2022

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 {{MitoFit page name}}
 {{Publication
-|title=Alencar MB, Ramos EV, Silber AM, Oliveira MF (2022) A unifying hypothesis for the extraordinary energy metabolism of bloodstream ''Trypanosoma brucei''. https://doi.org/10.26124/mitofit:2022-0009
+|title=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
 |info=MitoFit Preprints 2022.9. [[File:MitoFit Preprints pdf.png|left|160px|link=https://wiki.oroboros.at/images/5/54/Alencar_2022_MitoFit.pdf|MitoFit pdf]] [https://wiki.oroboros.at/images/5/54/Alencar_2022_MitoFit.pdf A unifying hypothesis for the extraordinary energy metabolism of bloodstream ''Trypanosoma brucei'']<br/>
-|authors=Alencar Mayke Bezerra, Ramos Emily V, Silber Ariel M, Oliveira Marcus F
+|authors=Alencar Mayke Bezerra, Ramos Emily V, Silber Ariel M, Zikova Alena, Oliveira Marcus F
-|year=2022-04-07
+|year=2022-07-07
 |journal=MitoFit Prep
-|abstract=[[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) 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.
+|abstract=Version 2 ('''v2''') '''2022-07-07''' [https://wiki.oroboros.at/images/5/54/Alencar_2022_MitoFit.pdf doi:10.26124/mitofit:2022-0009.v2]
+::: <small>Version 1 ('''v1''') 2022-04-07 [https://wiki.oroboros.at/images/archive/5/54/20220707123437%21Alencar_2022_MitoFit.pdf doi:10.26124/mitofit:2022-0009.v1] - [https://wiki.oroboros.at/index.php/File:Alencar_2022_MitoFit.pdf »Link to all versions«]</small>
+[[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
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 |mipnetlab=BR Sao Paulo Silber AM, BR Rio de Janeiro Oliveira MF
 }}
-ORC'''ID''': [[File:ORCID.png|20px|link=https://orcid.org/0000-0001-9145-7994]] Alencar MB, [[File:ORCID.png|20px|link=https://orcid.org/0000-0003-4528-4732]] Silber Ariel M, [[File:ORCID.png|20px|link=https://orcid.org/0000-0002-9890-8425]] Oliveira Marcus F
+ORC'''ID''': [[File:ORCID.png|20px|link=https://orcid.org/0000-0001-9145-7994]] Alencar MB, [[File:ORCID.png|20px|link=https://orcid.org/0000-0003-4528-4732]] Silber Ariel M, [[File:ORCID.png|20px|link=https://orcid.org/0000-0002-8686-0225]]  Zikova Alena, [[File:ORCID.png|20px|link=https://orcid.org/0000-0002-9890-8425]] Oliveira Marcus F
 {{Labeling