p62 Stages an Interplay Between the Ubiquitin-Proteasome System and Autophagy in the Heart of Defense Against Proteotoxic Stress

As exemplified by desmin-related cardiomyopathy and myocardial ischemia/reperfusion injury, proteasome functional insufficiency plays an essential pathogenic role in the progression of cardiac diseases with elevated proteotoxic stress. Upregulation of p62/SQSTM1 and increased selective autophagy in cardiomyocytes may protect against proteotoxic stress in the heart. p62 may serve as a proteotoxic stress sensor, promote segregation and degradation of misfolded proteins by autophagy, and mediate the cross talk between the ubiquitin-proteasome system and autophagy.