TY - JOUR
T1 - Mir-1 coordinately regulates lysosomal v-atpase and biogenesis to impact proteotoxicity and muscle function during aging
AU - Schiffer, Isabelle
AU - Gerisch, Birgit
AU - Kawamura, Kazuto
AU - Laboy, Raymond
AU - Hewitt, Jennifer
AU - Denzel, Martin Sebastian
AU - Mori, Marcelo A.
AU - Vanapalli, Siva
AU - Shen, Yidong
AU - Symmons, Orsolya
AU - Antebi, Adam
N1 - Publisher Copyright:
©Schiffer et al.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85111437709&partnerID=8YFLogxK
U2 - 10.7554/eLife.66768
DO - 10.7554/eLife.66768
M3 - Article
C2 - 34311841
AN - SCOPUS:85111437709
SN - 2050-084X
VL - 10
JO - eLife
JF - eLife
M1 - e66768
ER -