Autophagy: Basic principles and relevance to disease

Autophagy is a process by which cytoplasmic components are sequestered in double membrane vesicles and degraded upon fusion with lysosomal compartments. In yeast, autophagy is activated in response to changes in the extracellular milieu. Depending upon the stimulus, autophagy can degrade cytoplasmic contents non-specifically or can target the degradation of specific cellular components. Both of these have been adopted in higher eukaryotes and account for the expanding role of autophagy in various cellular processes, as well as contribute to the variation in cellular outcomes after induction of autophagy. In some cases, autophagy appears to be an adaptive response, whereas tinder other circumstances it is involved in cell death. In mammals, autophagy has been implicated in either the pathogenesis or response to a wide variety of diseases, including neurodegenerative disease, chronic bacterial and viral infections, atherosclerosis, and cancer. As the basic molecular pathways that regulate autophagy are elucidated, the relationship of autophagy to the pathogenesis of various disease states emerges.