Autophagy regulation and integration with cell signaling.

SIGNIFICANCE: Study over the past decade has revealed the critical role of autophagy in homeostatic and stress cell signaling. Autophagy is an intracellular process whereby double-membrane structures termed autophagosomes deliver cellular components to lysosomes for their degradation.

RECENT ADVANCES: Targets of specific autophagy range from proteins to protein aggregates to organelles and intracellular pathogens. Accordingly, autophagy fulfills numerous physiological roles and its deregulation can underlie disease.

CRITICAL ISSUES: Although autophagy is orchestrated by common core machinery, the discovery of distinct and highly varied autophagic programs reveals autophagy as a heterogeneous phenomenon, capable of specificity.

FUTURE DIRECTIONS: Here the molecular mechanisms of mammalian autophagy are reviewed, including recent advances in unraveling of its machinery, specificity, and regulation. With our increasing knowledge of autophagy mechanisms and signaling roles, we begin to work towards a systems understanding of autophagy.