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

eLife

Siva Vanapalli¹  Martin Sebastian Denzel²  Orsolya Symmons³  Adam Antebi⁴  Yidong Shen⁵  Raymond Laboy⁶  Isabelle Schiffer⁶  Kazuto Kawamura⁶  Birgit Gerisch⁶  Marcelo A Mori⁶  Jennifer Hewitt⁶ 

[1] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany;Department of Chemical Engineering, Texas Tech University, Lubbock, United States;Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil;Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil;Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil;Max Planck Institute for Biology of Ageing, Cologne, Germany;

关键词: miR-1;    lysosomal v-ATPase;    vha-13;    polyglutamine;    proteostasis;   

DOI  :  10.7554/eLife.66768

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown