Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis.

ABSTRACT: Mutations in lamin A (LMNA) are responsible for a variety of human dystrophic and metabolic diseases. Here, we created a mouse model in which progerin, the lamin A mutant protein that causes Hutchinson-Gilford progeria syndrome (HGPS), can be inducibly overexpressed. Muscle-specific overexpression of progerin was sufficient to induce muscular dystrophy and alter whole-body energy expenditure, leading to premature death. Intriguingly, sarcolipin (Sln), an endoplasmic reticulum (ER)-associated protein involved in heat production, is upregulated in progerin-expressing and Lmna knockout (Lmna^-/- ) skeletal muscle. The depletion of Sln accelerated the early death of Lmna^-/- mice. An examination at the molecular level revealed that progerin recruits Sln and Calnexin to the

SUBMITTER: Wang WP 

PROVIDER: S-EPMC6996945 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature