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Here, we created a mouse model in which progerin, the lamin A mutant protein that causes Hutchinson\u2013Gilford progeria syndrome (HGPS), can be inducibly overexpressed. Muscle\u2010specific overexpression of progerin was sufficient to induce muscular dystrophy and alter whole\u2010body energy expenditure, leading to premature death. Intriguingly, sarcolipin (Sln), an endoplasmic reticulum (ER)\u2010associated protein involved in heat production, is upregulated in progerin\u2010expressing and <jats:italic>Lmna<\/jats:italic> knockout (<jats:italic>Lmna<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) skeletal muscle. The depletion of <jats:italic>Sln<\/jats:italic> accelerated the early death of <jats:italic>Lmna<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. An examination at the molecular level revealed that progerin recruits Sln and Calnexin to the nuclear periphery. Furthermore, progerin\u2010expressing myoblasts presented enhanced store\u2010operated Ca<jats:sup>2+<\/jats:sup> entry, as well as increased co\u2010localization of STIM1 and ORAI1. These findings suggest that progerin dysregulates calcium homeostasis through an interaction with a subset of ER\u2010associated proteins, resulting in thermogenic and metabolic abnormalities.<\/jats:p>","DOI":"10.1111\/acel.13090","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T06:10:21Z","timestamp":1576217421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis"],"prefix":"10.1111","volume":"19","author":[{"given":"Wan\u2010Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Zhunan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Ya","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Pharmaceutical 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