Cardioprotection requires taking out the trash

Autophagy is a critical cellular housekeeping process that is essential for removal of damaged or unwanted organelles and protein aggregates. Under conditions of starvation, it is also a mechanism to break down proteins to generate amino acids for synthesis of new and more urgently needed proteins. In the heart, autophagy is upregulated by starvation, reactive oxygen species, hypoxia, exercise, and ischemic preconditioning, the latter a well-known potent cardioprotective phenomenon. The observation that upregulation of autophagy confers protection against ischemia/reperfusion injury and inhibition of autophagy is associated with a loss of cardioprotection conferred by pharmacological conditioning suggests that the pathway plays a key role in enhancing the heart's tolerance to ischemia. While many of the antecedent signaling pathways of preconditioning are well-defined, the mechanisms by which preconditioning and autophagy converge to protect the heart are unknown. In this review we discuss mechanisms that potentially underlie the linkage between cardioprotection and autophagy in the heart.