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

Author(s):Show less -

Schiffer, Isabelle ^[1] ; Gerisch, Birgit ^[1] ; Kawamura, Kazuto ^[1] ; Laboy, Raymond ^[1] ; Hewitt, Jennifer ^{[1, 2]} ; Denzel, Martin Sebastian ^{[1, 3]} ; Mori, Marcelo A. ^{[4, 5, 6]} ; Vanapalli, Siva ^[2] ; Shen, Yidong ^[7] ; Symmons, Orsolya ^[1] ; Antebi, Adam ^{[1, 3]}

Affiliation

^[1] Max Planck Inst Biol Ageing, Cologne - Germany

^[2] Texas Tech Univ, Dept Chem Engn, Lubbock, TX 79409 - USA

^[3] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, Cologne - Germany

^[4] Univ Estadual Campinas, Dept Biochem & Tissue Biol, Lab Aging Biol, UNICAMP, Campinas - Brazil

^[5] Univ Estadual Campinas, Expt Med Res Cluster EMRC, UNICAMP, Campinas - Brazil

^[6] Univ Estadual Campinas, Obes & Comorbid Res Ctr OCRC, UNICAMP, Campinas - Brazil

^[7] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Innovat Ctr Cel, State Key Lab Cell Biol, CAS Ctr Excellence Mol Ce, Shanghai - Peoples R China

• Document type: Journal article
• Source: eLIFE; v. 10, JUL 27 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 19/25958-9 - DecAI: decoding aging initiative
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Regular Research Grants