Autophagy as a therapeutic target for ischaemia/reperfusion injury? Concepts, controversies, and challenges

Autophagy is the tightly orchestrated cellular 'housekeeping' process responsible for the degradation and disposal of damaged and dysfunctional organelles and protein aggregates. In addition to its established basal role in the maintenance of normal cellular phenotype and function, there is growing interest in the concept that targeted modulation of autophagy under conditions of stress (most notably, ischaemia/reperfusion) may represent an adaptive mechanism and render the myocardium resistant to ischaemia/reperfusion injury. Our aims in this review are to: (i) provide a balanced overview of the emerging hypothesis that perturbation of autophagy may serve as a novel, intriguing, and powerful cardioprotective treatment strategy and (ii) summarize the controversies and challenges in exploiting autophagy as a therapeutic target for ischaemia/reperfusion injury.