The interplay between cell death signaling pathways in the heart

To date, one of the most intriguing and compelling concepts to impact contemporary cell biology is the notion that cell fate is “programmed” or genetically controlled. Indeed, the regulation of cell fate is crucial for embryonic development, and tissue homeostasis. Given the importance of removing damaged or irreversibly injured cells from the body, it is not surprising that defects in the regulatory mechanisms that govern cell death and/or survival more generally have been implicated in a number of human pathologies including cancer, neurodegenerative diseases, and cardiac failure. Several processes involved in the regulation of cell fate through apoptosis, necrosis, and autophagy are commonly linked through the actions of certain Bcl-2 proteins that act on the mitochondrion. For example, the Bcl-2 protein Beclin-1 is actively involved in the clearance of damaged mitochondria via mitophagy, while other Bcl-2 proteins such as Bax/Bak can initiate apoptosis or necrotic signaling pathways. The overlapping and redundant nature of these proteins highlights their evolutionary importance for regulating cardiac cell survival and death during normal and disease states. Here, we explore the interrelationship between these signaling pathways and the cellular effectors that influence cardiac cell fate.