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miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging

One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria; however, the regulato...

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Autores principales: Goljanek‐Whysall, Katarzyna, Soriano‐Arroquia, Ana, McCormick, Rachel, Chinda, Caroline, McDonagh, Brian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189996/
https://www.ncbi.nlm.nih.gov/pubmed/32291905
http://dx.doi.org/10.1111/acel.13140
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author Goljanek‐Whysall, Katarzyna
Soriano‐Arroquia, Ana
McCormick, Rachel
Chinda, Caroline
McDonagh, Brian
author_facet Goljanek‐Whysall, Katarzyna
Soriano‐Arroquia, Ana
McCormick, Rachel
Chinda, Caroline
McDonagh, Brian
author_sort Goljanek‐Whysall, Katarzyna
collection PubMed
description One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria; however, the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during aging concomitant with dysregulation of miR‐181a target interactions. Using functional approaches and mito‐QC assay, we have established that miR‐181a is an endogenous regulator of mitochondrial dynamics through concerted regulation of Park2, p62/SQSTM1, and DJ‐1 in vitro. Downregulation of miR‐181a with age was associated with an accumulation of autophagy‐related proteins and abnormal mitochondria. Restoring miR‐181a levels in old mice prevented accumulation of p62, DJ‐1, and PARK2, and improved mitochondrial quality and muscle function. These results provide physiological evidence for the potential of microRNA‐based interventions for age‐related muscle atrophy and of wider significance for diseases with disrupted mitochondrial dynamics.
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spelling pubmed-71899962020-04-30 miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging Goljanek‐Whysall, Katarzyna Soriano‐Arroquia, Ana McCormick, Rachel Chinda, Caroline McDonagh, Brian Aging Cell Original Articles One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria; however, the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during aging concomitant with dysregulation of miR‐181a target interactions. Using functional approaches and mito‐QC assay, we have established that miR‐181a is an endogenous regulator of mitochondrial dynamics through concerted regulation of Park2, p62/SQSTM1, and DJ‐1 in vitro. Downregulation of miR‐181a with age was associated with an accumulation of autophagy‐related proteins and abnormal mitochondria. Restoring miR‐181a levels in old mice prevented accumulation of p62, DJ‐1, and PARK2, and improved mitochondrial quality and muscle function. These results provide physiological evidence for the potential of microRNA‐based interventions for age‐related muscle atrophy and of wider significance for diseases with disrupted mitochondrial dynamics. John Wiley and Sons Inc. 2020-04-15 2020-04 /pmc/articles/PMC7189996/ /pubmed/32291905 http://dx.doi.org/10.1111/acel.13140 Text en © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Goljanek‐Whysall, Katarzyna
Soriano‐Arroquia, Ana
McCormick, Rachel
Chinda, Caroline
McDonagh, Brian
miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging
title miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging
title_full miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging
title_fullStr miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging
title_full_unstemmed miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging
title_short miR‐181a regulates p62/SQSTM1, parkin, and protein DJ‐1 promoting mitochondrial dynamics in skeletal muscle aging
title_sort mir‐181a regulates p62/sqstm1, parkin, and protein dj‐1 promoting mitochondrial dynamics in skeletal muscle aging
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189996/
https://www.ncbi.nlm.nih.gov/pubmed/32291905
http://dx.doi.org/10.1111/acel.13140
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