1. miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging
- Author
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Adam Antebi, Martin S. Denzel, Orsolya Symmons, Raymond Laboy, Yidong Shen, Kazuto Kawamura, Siva A. Vanapalli, Marcelo A. Mori, Birgit Gerisch, Jennifer E. Hewitt, and Isabelle Schiffer
- Subjects
0301 basic medicine ,Vacuolar Proton-Translocating ATPases ,QH301-705.5 ,Pharyngeal pumping ,Science ,Longevity ,Motility ,General Biochemistry, Genetics and Molecular Biology ,lysosomal v-ATPase ,vha-13 ,03 medical and health sciences ,0302 clinical medicine ,Animals ,V-ATPase ,Biology (General) ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Cell Nucleus ,proteostasis ,General Immunology and Microbiology ,biology ,Muscles ,General Neuroscience ,Genetics and Genomics ,General Medicine ,biology.organism_classification ,miR-1 ,Cell biology ,MicroRNAs ,030104 developmental biology ,Proteostasis ,Proteotoxicity ,Mutation ,C. elegans ,Medicine ,TFEB ,Lysosomes ,polyglutamine ,030217 neurology & neurosurgery ,Biogenesis ,Research Article - Abstract
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.
- Published
- 2021
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