mTORC2-Akt signaling axis is implicated in myocardial compensation and fibrosis

J Biol Regul Homeost Agents. 2015 Oct-Dec;29(4):745-53.

Abstract

mTOR signaling has long been implicated in the mechanisms of cardiomyocyte survival in response to volume or pressure overload. Several studies have focused on the significance of mTORC1 in cardiomyocyte survival, questioning the role of mTORC2. mTORC2–Akt signaling is an emerging axis implicated in cardiomyocyte compensation and thus heart failure. Upon being subjected to chronic stress, cardiomyocytes activate mTORC2–Akt signaling pathway to promote survival by activating the ubiquitin proteasome system, inducing the degradation of pro-apoptotic proteins, and altering the actin cytoskeleton. Given the importance of mTORC2 in cardiomyocyte survival, studies suggest that loss of mTORC2 signaling would result in loss of cardiomyocytes, fibrosis, and heart failure. This review serves to elaborate on how mTORC2-Akt signaling plays a role in cardiomyocyte growth and survival under stress and how the loss of the axis would result in fibrosis and heart failure.

Publication types

  • Editorial
  • Review

MeSH terms

  • Actins / metabolism
  • Cell Survival
  • Fibrosis
  • Heart Failure / etiology*
  • Humans
  • Mechanistic Target of Rapamycin Complex 2
  • Multiprotein Complexes / physiology*
  • Myocardium / pathology*
  • Myocytes, Cardiac / pathology
  • Proteasome Endopeptidase Complex / physiology
  • Proto-Oncogene Proteins c-akt / physiology*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Actins
  • Multiprotein Complexes
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Proteasome Endopeptidase Complex