Universität zu Köln

Schiffer, Isabelle, Gerisch, Birgit, Kawamura, Kazuto ORCID: 0000-0002-0376-7739, Laboy, Raymond ORCID: 0000-0002-0375-1550, Hewitt, Jennifer ORCID: 0000-0002-8798-1811, Denzel, Martin Sebastian, Mori, Marcelo A., Vanapalli, Siva, Shen, Yidong, Symmons, Orsolya ORCID: 0000-0003-2435-4236 and Antebi, Adam (2021). miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging. eLife, 10. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schiffer, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerisch, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawamura, Kazuto UNSPECIFIED orcid.org/0000-0002-0376-7739 UNSPECIFIED Laboy, Raymond UNSPECIFIED orcid.org/0000-0002-0375-1550 UNSPECIFIED Hewitt, Jennifer UNSPECIFIED orcid.org/0000-0002-8798-1811 UNSPECIFIED Denzel, Martin Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mori, Marcelo A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanapalli, Siva UNSPECIFIED UNSPECIFIED UNSPECIFIED Shen, Yidong UNSPECIFIED UNSPECIFIED UNSPECIFIED Symmons, Orsolya UNSPECIFIED orcid.org/0000-0003-2435-4236 UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-595610
DOI:	10.7554/eLife.66768
Journal or Publication Title:	eLife
Volume:	10
Date:	2021
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS; MICRORNAS; AUTOPHAGY; EXPRESSION; TARGETS; SWITCH; ROLES Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59561