Fig. 1: Schematic overview of autophagy induction with a focus on lipid involvement in signaling regulation.
From: Lipids associated with autophagy: mechanisms and therapeutic targets
mTORC1, a key suppressor of autophagy, is inhibited by AMPK under conditions promoting autophagy. AMPK also activates the ULK1/2 complex, which consists of ULK1/2, Atg13, FIP200, and Atg101. Upon activation, the ULK1/2 complex stimulates the PI3KC3 complex I, composed of VPS15, Beclin1, VPS34, and ATG14L. This complex regulates the production of phosphatidylinositol-3-phosphate (PI3P) on the phagophore, a crucial lipid that signals the progression of autophagy. Further downstream, lipids play an essential role in conjugating phosphatidylethanolamine (PE) to LC3, facilitating the formation of the autophagosome. The conjugation of LC3 with PE ensures membrane expansion and curvature necessary for autophagosome maturation, emphasizing the critical roles of lipids in both signal propagation and structural development during autophagy.
