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

eLife

Siva Vanapalli¹  Marcelo A Mori²  Orsolya Symmons³  Kazuto Kawamura³  Raymond Laboy³  Isabelle Schiffer³  Birgit Gerisch³  Adam Antebi⁴  Martin Sebastian Denzel⁴  Jennifer Hewitt⁵  Yidong Shen⁶ 

[1] Department of Chemical Engineering, Texas Tech University, Lubbock, United States;Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil;Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil;Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil;Max Planck Institute for Biology of Ageing, Cologne, Germany;Max Planck Institute for Biology of Ageing, Cologne, Germany;Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany;Max Planck Institute for Biology of Ageing, Cologne, Germany;Department of Chemical Engineering, Texas Tech University, Lubbock, United States;State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China;

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

DOI  :  10.7554/eLife.66768

来源: eLife Sciences Publications, Ltd

【 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】

CC BY