Molecular mechanisms and physiological significance of autophagy during myocardial ischemia and reperfusion

Abstract

Autophagy is an intracellular bulk degradation process whereby cytoplasmic proteins and organelles are degraded and recycled through lysosomes. In the heart, autophagy plays a homeostatic role at basal levels, and the absence of autophagy causes cardiac dysfunction and the development of cardiomyopathy. Autophagy is induced during myocardial ischemia and further enhanced by reperfusion. Although induction of autophagy during the ischemic phase is protective, further enhancement of autophagy during the reperfusion phase may induce cell death and appears to be detrimental. In this review we discuss the functional significance of autophagy and the underlying signaling mechanism in the heart during ischemia/reperfusion.

Figure 1

Hypothetical scheme describing the mechanism of autophagy under ischemia and reperfusion. Under ischemia, O₂ and nutrient supplies are decreased and the intracellular ATP level is reduced, causing activation of AMPK. These stimuli lead to autophagy, which may be protective. On the other hand, upon reperfusion, activation of AMPK is no longer observed. Instead, expression of Beclin 1 is markedly upregulated. Simultaneously, increased oxidative stress and ER stress may occur. These stimuli induce autophagy, which could be detrimental.