Fig. 2: Schematic overview of the major steps of autophagy with a focus on lipid involvement.
From: Lipids associated with autophagy: mechanisms and therapeutic targets
Atg proteins bind to PI3P on the phagophore surface, initiating the process. The Atg9-Atg2-Atg18 complex mediates lipid transfer from the ER to the growing phagophore, facilitating its elongation. Lipids play a critical role in regulating autophagy signaling at this stage. SQSTM1, with preselected cargo attached, binds to LC3-PE on the inner surface of the forming autophagosome. During autophagosome maturation, MTMR3 dephosphorylates PI3P, leading to the dissociation of Atg proteins, which is crucial for the autophagosome to become fusion-competent. Finally, lysosomes fuse with the matured autophagosome to form an autolysosome, where lipids and other cellular components undergo degradation in the final phase of autophagy.
