Difference between revisions of "Oliveira 2022 Abstract Bioblast"

Latest revision as of 09:46, 16 June 2022

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 »MitoFit Preprint«

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 F₁F_O 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 A^2,3, Oliveira MF^4,5

Laboratory of Biochemistry of Trypanosomatids - LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branišovská 31, 37005, České Budějovice, Czech Republic
Faculty of Science, University of South Bohemia, Branišovská 31, 37005, České Budějovice, Czech Republic
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
Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil - [email protected]

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+[[File:Bioblast2022 banner.jpg|link=Bioblast_2022]]
 {{Abstract
-|title=[[File:OliveiraM.jpg|left|100px|Oliveira Marcus F]]  Alencar MB, Ramos EV, Silber AM, <u>Oliveira Marcus F</u> (2022) A unifying hypothesis for the extraordinary energy metabolism of bloodstream ''Trypanosoma brucei''. Bioblast 2022: BEC Inaugural Conference.
+|title=[[File:OliveiraM.jpg|left|100px|Oliveira Marcus F]]  Alencar MB, Ramos EV, Silber AM, Zikova A, <u>Oliveira Marcus F</u> (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 <br>[[Alencar 2022 MitoFit|»''MitoFit Preprint''«]]
 |info=[https://wiki.oroboros.at/index.php/Bioblast_2022#Submitted_abstracts Bioblast 2022: BEC Inaugural Conference]
-|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
 |event=[[Bioblast 2022]]
-|abstract=
+|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)  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 F<sub>1</sub>F<sub>O</sub> 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.
-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. <br>
 |keywords=Alternative oxidase; glycerol phosphate; reactive oxygen species; cell death; ''Trypanosoma brucei''; mitophagy; antioxidant
 |editor=
 |mipnetlab=BR Sao Paulo Silber AM, BR Rio de Janeiro Oliveira MF
 }}
 == Affiliations ==
-:::: Alencar MB(1), Ramos EV(1), Silber AM(1), Oliveira MF(2,3)
+:::: Alencar MB<sup>1</sup>, Ramos EV<sup>1</sup>, Silber AM<sup>1</sup>,  Zíková  A<sup>2,3</sup>, Oliveira MF<sup>4,5</sup>
-::::#Laboratory of Biochemistry of Trypanosomatids - LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
+::::# Laboratory of Biochemistry of Trypanosomatids - LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
-::::#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
+::::#  Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branišovská 31, 37005, České Budějovice, Czech Republic
-::::#Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil - [email protected]
+::::#  Faculty of Science, University of South Bohemia, Branišovská 31, 37005, České Budějovice, Czech Republic
+::::# 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
+::::# Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil - [email protected]
-== Help ==
+== List of abbreviations, terms and definitions - MitoPedia ==
-* [[MitoPedia: Terms and abbreviations]]
+{{Template:List of abbreviations, terms and definitions - MitoPedia}}
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