Antagonistic functions of LMNA isoforms in energy expenditure and lifespan.

Détails

ID Serval
serval:BIB_F93AC620BB91
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Antagonistic functions of LMNA isoforms in energy expenditure and lifespan.
Périodique
Embo Reports
Auteur(s)
Lopez-Mejia I.C., de Toledo M., Chavey C., Lapasset L., Cavelier P., Lopez-Herrera C., Chebli K., Fort P., Beranger G., Fajas L., Amri E.Z., Casas F., Tazi J.
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
15
Numéro
5
Pages
529-539
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish PDF : Scientific Report
Résumé
Alternative RNA processing of LMNA pre-mRNA produces three main protein isoforms, that is, lamin A, progerin, and lamin C. De novo mutations that favor the expression of progerin over lamin A lead to Hutchinson-Gilford progeria syndrome (HGPS), providing support for the involvement of LMNA processing in pathological aging. Lamin C expression is mutually exclusive with the splicing of lamin A and progerin isoforms and occurs by alternative polyadenylation. Here, we investigate the function of lamin C in aging and metabolism using mice that express only this isoform. Intriguingly, these mice live longer, have decreased energy metabolism, increased weight gain, and reduced respiration. In contrast, progerin-expressing mice show increased energy metabolism and are lipodystrophic. Increased mitochondrial biogenesis is found in adipose tissue from HGPS-like mice, whereas lamin C-only mice have fewer mitochondria. Consistently, transcriptome analyses of adipose tissues from HGPS and lamin C-only mice reveal inversely correlated expression of key regulators of energy expenditure, including Pgc1a and Sfrp5. Our results demonstrate that LMNA encodes functionally distinct isoforms that have opposing effects on energy metabolism and lifespan in mammals.
Pubmed
Web of science
Création de la notice
20/06/2014 18:32
Dernière modification de la notice
03/03/2018 22:53
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