ATG13ULK1

ATG13ULK1 refers to the functional core of the autophagy initiation machinery formed by the interaction of ATG13 and ULK1, two central autophagy-related proteins. In mammals, ULK1 forms a core complex with ATG13, FIP200 (RB1CC1), and ATG101, with ATG13 serving as a regulatory hub that binds ULK1 and influences its kinase activity. The ULK1-ATG13 axis is evolutionarily conserved, reflecting a shared mechanism for triggering autophagy in response to cellular stress.

The complex integrates nutrient and energy signals to regulate autophagy. mTORC1 inhibits ULK1 under nutrient-rich conditions, preventing autophagy, while AMPK activates ULK1 during energy stress or starvation, promoting autophagosome formation. Activation leads ULK1 to phosphorylate substrates including ATG13 and FIP200, facilitating recruitment of downstream autophagy machinery to the phagophore assembly site and initiation of autophagosome biogenesis. ATG13 contributes to complex stability and activity through phosphorylation-dependent regulation, acting as a scaffold that modulates signal transmission to ULK1.

Physiological roles of the ATG13-ULK1 axis include cellular quality control, turnover of damaged organelles, and adaptation to nutrient deprivation. Dysregulation of ULK1-ATG13 signaling has been linked to diseases where autophagy plays a role, such as cancer, neurodegenerative disorders, and infectious diseases. Therapeutic strategies aiming to modulate ULK1 activity are under investigation, though achieving specificity and context-dependent outcomes remains a challenge.

See also: autophagy, ULK1, ATG13, FIP200, ATG101.