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Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia

Rapid adaptation to extreme hypoxia is a challenging problem, and there is no effective scheme to achieve rapid adaptation to extreme hypoxia. In this study, we found that withaferin A (WA) can significantly reduce myocardial damage, maintain cardiac function, and improve survival in rats in extreme...

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Autores principales: Zhao, Ruzhou, Xu, Yixin, Wang, Xiaobo, Zhou, Xiang, Liu, Yanqi, Jiang, Shuai, Zhang, Lin, Yu, Zhibin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818179/
https://www.ncbi.nlm.nih.gov/pubmed/36611879
http://dx.doi.org/10.3390/cells12010085
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author Zhao, Ruzhou
Xu, Yixin
Wang, Xiaobo
Zhou, Xiang
Liu, Yanqi
Jiang, Shuai
Zhang, Lin
Yu, Zhibin
author_facet Zhao, Ruzhou
Xu, Yixin
Wang, Xiaobo
Zhou, Xiang
Liu, Yanqi
Jiang, Shuai
Zhang, Lin
Yu, Zhibin
author_sort Zhao, Ruzhou
collection PubMed
description Rapid adaptation to extreme hypoxia is a challenging problem, and there is no effective scheme to achieve rapid adaptation to extreme hypoxia. In this study, we found that withaferin A (WA) can significantly reduce myocardial damage, maintain cardiac function, and improve survival in rats in extremely hypoxic environments. Mechanistically, WA protects against extreme hypoxia by affecting BCL2-interacting protein 3 (BNIP3)-mediated mitophagy and the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)-mediated mitochondrial biogenesis pathway among mitochondrial quality control mechanisms. On the one hand, enhanced mitophagy eliminates hypoxia-damaged mitochondria and prevents the induction of apoptosis; on the other hand, enhanced mitochondrial biogenesis can supplement functional mitochondria and maintain mitochondrial respiration to ensure mitochondrial ATP production under acute extreme hypoxia. Our study shows that WA can be used as an effective drug to improve tolerance to extreme hypoxia.
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spelling pubmed-98181792023-01-07 Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia Zhao, Ruzhou Xu, Yixin Wang, Xiaobo Zhou, Xiang Liu, Yanqi Jiang, Shuai Zhang, Lin Yu, Zhibin Cells Article Rapid adaptation to extreme hypoxia is a challenging problem, and there is no effective scheme to achieve rapid adaptation to extreme hypoxia. In this study, we found that withaferin A (WA) can significantly reduce myocardial damage, maintain cardiac function, and improve survival in rats in extremely hypoxic environments. Mechanistically, WA protects against extreme hypoxia by affecting BCL2-interacting protein 3 (BNIP3)-mediated mitophagy and the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)-mediated mitochondrial biogenesis pathway among mitochondrial quality control mechanisms. On the one hand, enhanced mitophagy eliminates hypoxia-damaged mitochondria and prevents the induction of apoptosis; on the other hand, enhanced mitochondrial biogenesis can supplement functional mitochondria and maintain mitochondrial respiration to ensure mitochondrial ATP production under acute extreme hypoxia. Our study shows that WA can be used as an effective drug to improve tolerance to extreme hypoxia. MDPI 2022-12-25 /pmc/articles/PMC9818179/ /pubmed/36611879 http://dx.doi.org/10.3390/cells12010085 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Ruzhou
Xu, Yixin
Wang, Xiaobo
Zhou, Xiang
Liu, Yanqi
Jiang, Shuai
Zhang, Lin
Yu, Zhibin
Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia
title Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia
title_full Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia
title_fullStr Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia
title_full_unstemmed Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia
title_short Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia
title_sort withaferin a enhances mitochondrial biogenesis and bnip3-mediated mitophagy to promote rapid adaptation to extreme hypoxia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818179/
https://www.ncbi.nlm.nih.gov/pubmed/36611879
http://dx.doi.org/10.3390/cells12010085
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