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The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders?
SIGNIFICANCE: The mitochondrial oxidative phosphorylation (OXPHOS) system, comprising the electron transport chain and ATP synthase, generates membrane potential, drives ATP synthesis, governs energy metabolism, and maintains redox balance. OXPHOS dysfunction is associated with a plethora of disease...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc., publishers
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398489/ https://www.ncbi.nlm.nih.gov/pubmed/34605675 http://dx.doi.org/10.1089/ars.2021.0137 |
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author | Gore, Emilia Duparc, Thibaut Genoux, Annelise Perret, Bertrand Najib, Souad Martinez, Laurent O. |
author_facet | Gore, Emilia Duparc, Thibaut Genoux, Annelise Perret, Bertrand Najib, Souad Martinez, Laurent O. |
author_sort | Gore, Emilia |
collection | PubMed |
description | SIGNIFICANCE: The mitochondrial oxidative phosphorylation (OXPHOS) system, comprising the electron transport chain and ATP synthase, generates membrane potential, drives ATP synthesis, governs energy metabolism, and maintains redox balance. OXPHOS dysfunction is associated with a plethora of diseases ranging from rare inherited disorders to common conditions, including diabetes, cancer, neurodegenerative diseases, as well as aging. There has been great interest in studying regulators of OXPHOS. Among these, ATPase inhibitory factor 1 (IF1) is an endogenous inhibitor of ATP synthase that has long been thought to avoid the consumption of cellular ATP when ATP synthase acts as an ATP hydrolysis enzyme. RECENT ADVANCES: Recent data indicate that IF1 inhibits ATP synthesis and is involved in a multitude of mitochondrial-related functions, such as mitochondrial quality control, energy metabolism, redox balance, and cell fate. IF1 also inhibits the ATPase activity of cell-surface ATP synthase, and it is used as a cardiovascular disease biomarker. CRITICAL ISSUES: Although recent data have led to a paradigm shift regarding IF1 functions, these have been poorly studied in entire organisms and in different organs. The understanding of the cellular biology of IF1 is, therefore, still limited. The aim of this review was to provide an overview of the current understanding of the role of IF1 in mitochondrial functions, health, and diseases. FUTURE DIRECTIONS: Further investigations of IF1 functions at the cell, organ, and whole-organism levels and in different pathophysiological conditions will help decipher the controversies surrounding its involvement in mitochondrial function and could unveil therapeutic strategies in human pathology. Antioxid. Redox Signal. 37, 370–393. |
format | Online Article Text |
id | pubmed-9398489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Mary Ann Liebert, Inc., publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-93984892022-08-24 The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? Gore, Emilia Duparc, Thibaut Genoux, Annelise Perret, Bertrand Najib, Souad Martinez, Laurent O. Antioxid Redox Signal Forum Review Articles SIGNIFICANCE: The mitochondrial oxidative phosphorylation (OXPHOS) system, comprising the electron transport chain and ATP synthase, generates membrane potential, drives ATP synthesis, governs energy metabolism, and maintains redox balance. OXPHOS dysfunction is associated with a plethora of diseases ranging from rare inherited disorders to common conditions, including diabetes, cancer, neurodegenerative diseases, as well as aging. There has been great interest in studying regulators of OXPHOS. Among these, ATPase inhibitory factor 1 (IF1) is an endogenous inhibitor of ATP synthase that has long been thought to avoid the consumption of cellular ATP when ATP synthase acts as an ATP hydrolysis enzyme. RECENT ADVANCES: Recent data indicate that IF1 inhibits ATP synthesis and is involved in a multitude of mitochondrial-related functions, such as mitochondrial quality control, energy metabolism, redox balance, and cell fate. IF1 also inhibits the ATPase activity of cell-surface ATP synthase, and it is used as a cardiovascular disease biomarker. CRITICAL ISSUES: Although recent data have led to a paradigm shift regarding IF1 functions, these have been poorly studied in entire organisms and in different organs. The understanding of the cellular biology of IF1 is, therefore, still limited. The aim of this review was to provide an overview of the current understanding of the role of IF1 in mitochondrial functions, health, and diseases. FUTURE DIRECTIONS: Further investigations of IF1 functions at the cell, organ, and whole-organism levels and in different pathophysiological conditions will help decipher the controversies surrounding its involvement in mitochondrial function and could unveil therapeutic strategies in human pathology. Antioxid. Redox Signal. 37, 370–393. Mary Ann Liebert, Inc., publishers 2022-08-01 2022-08-01 /pmc/articles/PMC9398489/ /pubmed/34605675 http://dx.doi.org/10.1089/ars.2021.0137 Text en © Emilia Gore et al., 2022; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by-nc/4.0/This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License [CC-BY-NC] (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited. |
spellingShingle | Forum Review Articles Gore, Emilia Duparc, Thibaut Genoux, Annelise Perret, Bertrand Najib, Souad Martinez, Laurent O. The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? |
title | The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? |
title_full | The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? |
title_fullStr | The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? |
title_full_unstemmed | The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? |
title_short | The Multifaceted ATPase Inhibitory Factor 1 (IF1) in Energy Metabolism Reprogramming and Mitochondrial Dysfunction: A New Player in Age-Associated Disorders? |
title_sort | multifaceted atpase inhibitory factor 1 (if1) in energy metabolism reprogramming and mitochondrial dysfunction: a new player in age-associated disorders? |
topic | Forum Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398489/ https://www.ncbi.nlm.nih.gov/pubmed/34605675 http://dx.doi.org/10.1089/ars.2021.0137 |
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