Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and impaired cardiac adaptation.

Journal Article (Journal Article)

Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (muscle enriched A-type lamin-interacting protein), a unique protein of unknown function, is required for proper cardiac adaptation. Mlip(-/-) mice exhibited normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of Akt/mTOR pathways. Cardiac-specific MLIP overexpression led to an inhibition of Akt/mTOR, providing evidence of a direct impact of MLIP on these key signaling pathways. Mlip(-/-) hearts showed an impaired capacity to adapt to stress (isoproterenol-induced hypertrophy), likely because of deregulated Akt/mTOR activity. Genome-wide association studies showed a genetic association between Mlip and early response to cardiac stress, supporting the role of MLIP in cardiac adaptation. Together, these results revealed that MLIP is required for normal myocardial adaptation to stress through integrated regulation of the Akt/mTOR pathways.

Full Text

Duke Authors

Cited Authors

  • Cattin, M-E; Wang, J; Weldrick, JJ; Roeske, CL; Mak, E; Thorn, SL; DaSilva, JN; Wang, Y; Lusis, AJ; Burgon, PG

Published Date

  • October 30, 2015

Published In

Volume / Issue

  • 290 / 44

Start / End Page

  • 26699 - 26714

PubMed ID

  • 26359501

Pubmed Central ID

  • PMC4646324

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M115.678433


  • eng

Conference Location

  • United States