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On the Origin of ATP Synthesis in Cancer

ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the ΔG′(ATP) hydrolysis of −56 kJ/mole is the endpoint of both genetic and metabolic processes required for life. Various anomalies in mitochondrial structure and function prevent max...

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Autores principales: Seyfried, Thomas N., Arismendi-Morillo, Gabriel, Mukherjee, Purna, Chinopoulos, Christos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677709/
https://www.ncbi.nlm.nih.gov/pubmed/33251492
http://dx.doi.org/10.1016/j.isci.2020.101761
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author Seyfried, Thomas N.
Arismendi-Morillo, Gabriel
Mukherjee, Purna
Chinopoulos, Christos
author_facet Seyfried, Thomas N.
Arismendi-Morillo, Gabriel
Mukherjee, Purna
Chinopoulos, Christos
author_sort Seyfried, Thomas N.
collection PubMed
description ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the ΔG′(ATP) hydrolysis of −56 kJ/mole is the endpoint of both genetic and metabolic processes required for life. Various anomalies in mitochondrial structure and function prevent maximal ATP synthesis through OxPhos in cancer cells. Little ATP synthesis would occur through glycolysis in cancer cells that express the dimeric form of pyruvate kinase M2. Mitochondrial substrate level phosphorylation (mSLP) in the glutamine-driven glutaminolysis pathway, substantiated by the succinate-CoA ligase reaction in the TCA cycle, can partially compensate for reduced ATP synthesis through both OxPhos and glycolysis. A protracted insufficiency of OxPhos coupled with elevated glycolysis and an auxiliary, fully operational mSLP, would cause a cell to enter its default state of unbridled proliferation with consequent dedifferentiation and apoptotic resistance, i.e., cancer. The simultaneous restriction of glucose and glutamine offers a therapeutic strategy for managing cancer.
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spelling pubmed-76777092020-11-27 On the Origin of ATP Synthesis in Cancer Seyfried, Thomas N. Arismendi-Morillo, Gabriel Mukherjee, Purna Chinopoulos, Christos iScience Review ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the ΔG′(ATP) hydrolysis of −56 kJ/mole is the endpoint of both genetic and metabolic processes required for life. Various anomalies in mitochondrial structure and function prevent maximal ATP synthesis through OxPhos in cancer cells. Little ATP synthesis would occur through glycolysis in cancer cells that express the dimeric form of pyruvate kinase M2. Mitochondrial substrate level phosphorylation (mSLP) in the glutamine-driven glutaminolysis pathway, substantiated by the succinate-CoA ligase reaction in the TCA cycle, can partially compensate for reduced ATP synthesis through both OxPhos and glycolysis. A protracted insufficiency of OxPhos coupled with elevated glycolysis and an auxiliary, fully operational mSLP, would cause a cell to enter its default state of unbridled proliferation with consequent dedifferentiation and apoptotic resistance, i.e., cancer. The simultaneous restriction of glucose and glutamine offers a therapeutic strategy for managing cancer. Elsevier 2020-11-02 /pmc/articles/PMC7677709/ /pubmed/33251492 http://dx.doi.org/10.1016/j.isci.2020.101761 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Seyfried, Thomas N.
Arismendi-Morillo, Gabriel
Mukherjee, Purna
Chinopoulos, Christos
On the Origin of ATP Synthesis in Cancer
title On the Origin of ATP Synthesis in Cancer
title_full On the Origin of ATP Synthesis in Cancer
title_fullStr On the Origin of ATP Synthesis in Cancer
title_full_unstemmed On the Origin of ATP Synthesis in Cancer
title_short On the Origin of ATP Synthesis in Cancer
title_sort on the origin of atp synthesis in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677709/
https://www.ncbi.nlm.nih.gov/pubmed/33251492
http://dx.doi.org/10.1016/j.isci.2020.101761
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