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Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy
Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality con...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449344/ https://www.ncbi.nlm.nih.gov/pubmed/34493662 http://dx.doi.org/10.1073/pnas.2025932118 |
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author | Drake, Joshua C. Wilson, Rebecca J. Laker, Rhianna C. Guan, Yuntian Spaulding, Hannah R. Nichenko, Anna S. Shen, Wenqing Shang, Huayu Dorn, Maya V. Huang, Kian Zhang, Mei Bandara, Aloka B. Brisendine, Matthew H. Kashatus, Jennifer A. Sharma, Poonam R. Young, Alexander Gautam, Jitendra Cao, Ruofan Wallrabe, Horst Chang, Paul A. Wong, Michael Desjardins, Eric M. Hawley, Simon A. Christ, George J. Kashatus, David F. Miller, Clint L. Wolf, Matthew J. Periasamy, Ammasi Steinberg, Gregory R. Hardie, D. Grahame Yan, Zhen |
author_facet | Drake, Joshua C. Wilson, Rebecca J. Laker, Rhianna C. Guan, Yuntian Spaulding, Hannah R. Nichenko, Anna S. Shen, Wenqing Shang, Huayu Dorn, Maya V. Huang, Kian Zhang, Mei Bandara, Aloka B. Brisendine, Matthew H. Kashatus, Jennifer A. Sharma, Poonam R. Young, Alexander Gautam, Jitendra Cao, Ruofan Wallrabe, Horst Chang, Paul A. Wong, Michael Desjardins, Eric M. Hawley, Simon A. Christ, George J. Kashatus, David F. Miller, Clint L. Wolf, Matthew J. Periasamy, Ammasi Steinberg, Gregory R. Hardie, D. Grahame Yan, Zhen |
author_sort | Drake, Joshua C. |
collection | PubMed |
description | Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5′ AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment. |
format | Online Article Text |
id | pubmed-8449344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-84493442021-10-04 Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy Drake, Joshua C. Wilson, Rebecca J. Laker, Rhianna C. Guan, Yuntian Spaulding, Hannah R. Nichenko, Anna S. Shen, Wenqing Shang, Huayu Dorn, Maya V. Huang, Kian Zhang, Mei Bandara, Aloka B. Brisendine, Matthew H. Kashatus, Jennifer A. Sharma, Poonam R. Young, Alexander Gautam, Jitendra Cao, Ruofan Wallrabe, Horst Chang, Paul A. Wong, Michael Desjardins, Eric M. Hawley, Simon A. Christ, George J. Kashatus, David F. Miller, Clint L. Wolf, Matthew J. Periasamy, Ammasi Steinberg, Gregory R. Hardie, D. Grahame Yan, Zhen Proc Natl Acad Sci U S A Biological Sciences Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5′ AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment. National Academy of Sciences 2021-09-14 2021-09-07 /pmc/articles/PMC8449344/ /pubmed/34493662 http://dx.doi.org/10.1073/pnas.2025932118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Drake, Joshua C. Wilson, Rebecca J. Laker, Rhianna C. Guan, Yuntian Spaulding, Hannah R. Nichenko, Anna S. Shen, Wenqing Shang, Huayu Dorn, Maya V. Huang, Kian Zhang, Mei Bandara, Aloka B. Brisendine, Matthew H. Kashatus, Jennifer A. Sharma, Poonam R. Young, Alexander Gautam, Jitendra Cao, Ruofan Wallrabe, Horst Chang, Paul A. Wong, Michael Desjardins, Eric M. Hawley, Simon A. Christ, George J. Kashatus, David F. Miller, Clint L. Wolf, Matthew J. Periasamy, Ammasi Steinberg, Gregory R. Hardie, D. Grahame Yan, Zhen Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
title | Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
title_full | Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
title_fullStr | Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
title_full_unstemmed | Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
title_short | Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
title_sort | mitochondria-localized ampk responds to local energetics and contributes to exercise and energetic stress-induced mitophagy |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449344/ https://www.ncbi.nlm.nih.gov/pubmed/34493662 http://dx.doi.org/10.1073/pnas.2025932118 |
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