Regulation of autophagy in the heart: "you only live twice".
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.
Aviv
Yaron
Y
Department of Pharmacology and Therapeutics, The Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
Shaw
James
J
Gang
Hongying
H
Kirshenbaum
Lorrie A
LA
D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010588:Phagosomes / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013312:Stress, Physiological
C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2