Mir-1 coordinately regulates lysosomal v-atpase and biogenesis to impact proteotoxicity and muscle function during aging

Isabelle Schiffer, Birgit Gerisch, Kazuto Kawamura, Raymond Laboy, Jennifer Hewitt, Martin Sebastian Denzel, Marcelo A. Mori, Siva Vanapalli, Yidong Shen, Orsolya Symmons, Adam Antebi

Research output: Contribution to journalArticlepeer-review

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 30 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.

Original languageEnglish
Article numbere66768
JournaleLife
Volume10
DOIs
StatePublished - Jul 2021

Fingerprint

Dive into the research topics of 'Mir-1 coordinately regulates lysosomal v-atpase and biogenesis to impact proteotoxicity and muscle function during aging'. Together they form a unique fingerprint.

Cite this