Autophagy as a regulated pathway of cellular degradation, 1365 Science 290

Macroautophagy is a dynamic process involving the rearrangement of subcellular membranes to sequester cytoplasm and organelles for delivery to the lysosome or vacuole where the sequestered cargo is degraded and recycled. This process takes place in all eukaryotic cells. It is highly regulated through the action of various kinases, phosphatases, and guanosine triphosphatases (GTPases). The core protein machinery that is necessary to drive formation and consumption of intermediates in the macroautophagy pathway includes a ubiquitin-like protein conjugation system and a protein complex that directs membrane docking and fusion at the lysosome or vacuole. Macroautophagy plays an important role in developmental processes, human disease, and cellular response to nutrient deprivation. Normal cell growth and developmentrequires a well-controlled balance be-tween protein synthesis and organelle biogenesis versus protein degradation and or-ganelle turnover. The major pathways for degradation of cellular constituents are auto-phagy and cytosolic turnover by the protea