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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...

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Autores principales: Schiffer, Isabelle, Gerisch, Birgit, Kawamura, Kazuto, Laboy, Raymond, Hewitt, Jennifer, Denzel, Martin Sebastian, Mori, Marcelo A, Vanapalli, Siva, Shen, Yidong, Symmons, Orsolya, Antebi, Adam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
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.
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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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