Regulation of autophagy in the heart: "you only live twice"

Abstract

Autophagy is a highly orchestrated cellular process by which proteins and organelles are degraded via an elaborate lysosomal pathway to generate free amino acids and sugars for ATP during metabolic stress. At present, the exact role of autophagy in the heart is highly debated but suggested to play a key role in regulating cell turnover in cardiomyopathies and heart failure. The signaling pathways and molecular effectors that govern autophagy are incomplete, as are the mechanisms that determine whether autophagy promotes or prevents cell death. The mitochondrion has been identified as a key organelle centrally involved in regulating autophagy. Certain members of the Bcl-2 gene family, including Beclin-1, Bcl-2 nineteen kilodaltons interacting protein (Bnip3), and Nix/Bnip3L, provoke mitochondrial perturbations leading to permeability transition pore opening, resulting in apoptosis, autophagy, or both. These and other aspects of autophagy processes have been discussed.