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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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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. |
format | Online Article Text |
id | pubmed-7677709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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