ATG12ATG5

ATG12-ATG5 is a covalently linked ubiquitin-like conjugate that plays a central role in autophagy. It is formed through a sequential enzyme cascade in which ATG12 is activated by the E1 enzyme ATG7 and transferred to the E2 enzyme ATG10, which then facilitates the conjugation of ATG12 to a lysine residue on ATG5 (Lys130 in human ATG5).

The ATG12-ATG5 conjugate subsequently binds ATG16L1 to form the ATG12-ATG5-ATG16L1 complex. This complex localizes to the pre-autophagosomal membrane and functions as an E3-like ligase that promotes the lipidation of LC3/ATG8 to phosphatidylethanolamine, a critical step for autophagosome membrane expansion and maturation.

Functionally, the ATG12-ATG5-ATG16L1 axis is essential for autophagosome formation and efficient autophagy. Disruption of any component impairs the lipidation cascade and autophagosome biogenesis. The complex is conserved across eukaryotes and operates within the broader autophagy machinery, coordinating with other core factors under nutrient stress and during selective autophagy processes.

Clinical and biological relevance includes associations between autophagy dysregulation and diseases such as cancer and neurodegenerative disorders, as well as roles in host defense against intracellular pathogens. Research ongoing in cell biology and pathology continues to clarify the precise regulatory networks and context-dependent functions of the ATG12-ATG5-ATG16L1 complex.