How is autophagosome formation regulated?

Autophagosome formation is a tightly regulated process involving several steps: 

• Generation of vesicles or autophagosomal membrane precursors
• Assembly of the vesicles to form the phagophore
• Elongation of the phagophore to complete the autophagosome

The autophagosomal membrane precursors are derived from various endomembrane compartments including endosomes, the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment, and ER-exit sites (ERES). During stress responses, early autophagosomal membrane precursors are produced by remodeling these endomembrane compartments. The phagophore assembly site (PAS), predominantly located on the ER, serves as the focal point for assembly and elongation of the autophagosomal membrane, and eventual autophagosome completion.

The orchestration of autophagosome formation involves ATG proteins, membrane remodeling factors, and autophagic membranes, all following a precise choreography. This coordination ensures the efficient progression of the autophagy process.