New insights into the mechanisms of macroautophagy in mammalian cells.

Macroautophagy is a self-digesting pathway responsible for the removal of long-lived proteins and organelles by the lysosomal compartment. Parts of the cytoplasm are first segregated in double-membrane-bound autophagosomes, which then undergo a multistep maturation process including fusion with endosomes and lysosomes. The segregated cytoplasm is then degraded by the lysosomal hydrolases. The discovery of ATG genes has greatly enhanced our understanding of the mechanisms of this pathway. Two novel ubiquitin-like protein conjugation systems were shown to function during autophagosome formation. Autophagy has been shown to play a role in a wide variety of physiological processes including energy metabolism, organelle turnover, growth regulation, and aging. Impaired autophagy can lead to diseases such as cardiomyopathy and cancer. This review summarizes current knowledge about the formation and maturation of autophagosomes, the role of macroautophagy in various physiological and pathological conditions, and the signaling pathways that regulate this process in mammalian cells.