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miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging
Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also plastic, and remodeled in response to stress, growth, neural and metabolic inputs. The conserved muscle-enriched microRNA, miR-1, regulate...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315803/ https://www.ncbi.nlm.nih.gov/pubmed/34311841 http://dx.doi.org/10.7554/eLife.66768 |
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author | Schiffer, Isabelle Gerisch, Birgit Kawamura, Kazuto Laboy, Raymond Hewitt, Jennifer Denzel, Martin Sebastian Mori, Marcelo A Vanapalli, Siva Shen, Yidong Symmons, Orsolya Antebi, Adam |
author_facet | Schiffer, Isabelle Gerisch, Birgit Kawamura, Kazuto Laboy, Raymond Hewitt, Jennifer Denzel, Martin Sebastian Mori, Marcelo A Vanapalli, Siva Shen, Yidong Symmons, Orsolya Antebi, Adam |
author_sort | Schiffer, Isabelle |
collection | PubMed |
description | Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also plastic, and remodeled in response to stress, growth, neural and metabolic inputs. The conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle development, but whether it plays a role during aging is unknown. Here we investigated Caenorhabditis elegans miR-1 in muscle function in response to proteostatic stress. mir-1 deletion improved mid-life muscle motility, pharyngeal pumping, and organismal longevity upon polyQ35 proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunit vha-13/ATP6V1A as a direct target downregulated via its 3′UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. Our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during aging. |
format | Online Article Text |
id | pubmed-8315803 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-83158032021-07-28 miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging Schiffer, Isabelle Gerisch, Birgit Kawamura, Kazuto Laboy, Raymond Hewitt, Jennifer Denzel, Martin Sebastian Mori, Marcelo A Vanapalli, Siva Shen, Yidong Symmons, Orsolya Antebi, Adam eLife Genetics and Genomics Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also plastic, and remodeled in response to stress, growth, neural and metabolic inputs. The conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle development, but whether it plays a role during aging is unknown. Here we investigated Caenorhabditis elegans miR-1 in muscle function in response to proteostatic stress. mir-1 deletion improved mid-life muscle motility, pharyngeal pumping, and organismal longevity upon polyQ35 proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunit vha-13/ATP6V1A as a direct target downregulated via its 3′UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. Our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during aging. eLife Sciences Publications, Ltd 2021-07-27 /pmc/articles/PMC8315803/ /pubmed/34311841 http://dx.doi.org/10.7554/eLife.66768 Text en © 2021, Schiffer et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Genetics and Genomics Schiffer, Isabelle Gerisch, Birgit Kawamura, Kazuto Laboy, Raymond Hewitt, Jennifer Denzel, Martin Sebastian Mori, Marcelo A Vanapalli, Siva Shen, Yidong Symmons, Orsolya Antebi, Adam miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging |
title | miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging |
title_full | miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging |
title_fullStr | miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging |
title_full_unstemmed | miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging |
title_short | miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging |
title_sort | mir-1 coordinately regulates lysosomal v-atpase and biogenesis to impact proteotoxicity and muscle function during aging |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315803/ https://www.ncbi.nlm.nih.gov/pubmed/34311841 http://dx.doi.org/10.7554/eLife.66768 |
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