Autophagy and Cell Death

Autophagy is an evolutionarily conserved biological phenomenon related to protein degradation and organelle turnover. Three types of autophagy have been defined: macroautophagy, microautophagy, and chaperone-mediated autophagy, which differ the way of in the delivery of substrates to the lysosome. In macroautophagy, substrates are wrapped in a double membrane structure, called the autophagosome. The formation of the autophagosome and its fusion with the lysosome are genetically controlled by a series of autophagy molecules and are activated in response to a number of environmental cues. Much has yet to be learned about the signaling pathway and the molecular mechanisms about this process. Autophagy is important to multiple cellular functions, particularly for nutrient and energy balance, and the turnover of cellular substances. The relationship of autophagy with cell death is complicated and may be context-dependent. Whereas the nature of autophagic death has yet to be carefully defined, it seems that autophagy may, in fact, be a key regulator of both apoptosis and necrosis. In this context, the roles of macroautophagy in both prosurvival and prodeath have been identified. Understanding the circumstance in which autophagy affects cell functions and therefore cell viability is critical for the future intervention of this process to control cancer, tissue injury, and other disease processes.