miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact 
proteotoxicity and muscle function during aging

Schiffer, I.; Gerisch, B.; Kawamura, K.; Laboy, R.; Hewitt, J.; Denzel, M.; Mori, M. A.; Vanapalli, S.; Shen, Y.; Symmons, O.; Antebi, Adam

doi:10.7554/eLife.66768

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miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging

MPS-Authors

/persons/resource/persons278123

Schiffer, I.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons130932

Gerisch, B.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278126

Kawamura, K.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278129

Laboy, R.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278132

Hewitt, J.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons179771

Denzel, M.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278135

Symmons, O.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons50070

Antebi, Adam
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/34311841
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引用

Schiffer, I., Gerisch, B., Kawamura, K., Laboy, R., Hewitt, J., Denzel, M., Mori, M. A., Vanapalli, S., Shen, Y., Symmons, O., & Antebi, A. (2021). miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging. Elife, 10. doi:10.7554/eLife.66768.

引用: https://hdl.handle.net/21.11116/0000-000A-FA4F-5

要旨

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.