Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development, and homeostasis. Autophagy  refers to any cellular degradative pathway that involves the delivery of cytoplasmic cargo to the lysosome. At least three forms have been identified—chaperone-mediated autophagy, microautophagy, and macroautophagy—that differ with respect to their physiological functions and the mode of cargo delivery to the lysosome.Autophagy occurs at low basal levels in virtually all cells to perform homeostatic functions such as protein and organelle turnover. One of the key regulators of autophagy is the target of rapamycin, TOR kinase, which is the major inhibitory signal that shuts off autophagy in the presence of growth factors and abundant nutrients. The class I PI3K/Akt signaling molecules link receptor tyrosine kinases to TOR activation and thereby repress autophagy in response to insulin-like and other growth factor signals.Some of the other regulatory molecules that control autophagy include 5′-AMP-activated protein kinase (AMPK), which responds to low energy; the eukaryotic initiation factor 2α (eIF2α), which responds to nutrient starvation, double-stranded RNA, and endoplasmic reticulum (ER) stress; BH3-only proteins that contain a Bcl-2 homology-3 (BH3) domain inhibition of the Beclin 1/class III PI3K and disrupt Bcl-2/Bcl-XL complex; the tumor suppressor protein, p53; death-associated protein kinases (DAPk); the ER-membrane-associated protein, Ire-1; the stress-activated kinase, c-Jun-N-terminal kinase; the inositoltrisphosphate (IP3) receptor (IP3R); GTPases; Erk1/2; ceramide; and calcium.

References

1.Levine B,et al. Cell. 2008 Jan 11;132(1):27-42.