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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9818179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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