The Role of Alternative Mitophagy in Heart Disease

Autophagy is essential for maintaining cellular homeostasis through bulk degradation of subcellular constituents, including misfolded proteins and dysfunctional organelles. It is generally governed by the proteins Atg5 and Atg7, which are critical regulators of the conventional autophagy pathway. However, recent studies have identified an alternative Atg5/Atg7-independent pathway, i.e., Ulk1- and Rab9-mediated alternative autophagy. More intensive studies have identified its essential role in stress-induced mitochondrial autophagy, also known as mitophagy. Alternative mitophagy plays pathophysiological roles in heart diseases such as myocardial ischemia and pressure overload. Here, this review discusses the established and emerging mechanisms of alternative autophagy/mitophagy that can be applied in therapeutic interventions for heart disorders.