ULK1-ATG13-FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy

ULK1-ATG13-FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy

Received for publication, January 27, 2009, and in revised form, February 26, 2009 Published, JBC Papers in Press, March 3, 2009, DOI 10.1074/jbc.M900573200 | Ian G. Ganley, Du H. Lam, Junru Wang, Xiaojun Ding, She Chen, and Xuejun Jiang
Autophagy is a cellular process that recycles long-lived and damaged components, and it is linked to various diseases and developmental processes. ULK1, a serine/threonine protein kinase, plays a crucial role in the initial stages of autophagy, but the exact molecular mechanism is not fully understood. This study identifies a novel protein complex containing ULK1, FIP200, and ATG13, which are essential for starvation-induced autophagy. Both FIP200 and ATG13 are critical for the correct localization of ULK1 to the pre-autophagosome and the stability of ULK1 protein. Additionally, FIP200 and ATG13 can enhance ULK1 kinase activity individually, but both are required for maximal stimulation. The study also shows that ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1·ATG13·FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis. The findings provide insights into the molecular regulation of ULK1 and the integration of autophagy signals in mammalian cells.Autophagy is a cellular process that recycles long-lived and damaged components, and it is linked to various diseases and developmental processes. ULK1, a serine/threonine protein kinase, plays a crucial role in the initial stages of autophagy, but the exact molecular mechanism is not fully understood. This study identifies a novel protein complex containing ULK1, FIP200, and ATG13, which are essential for starvation-induced autophagy. Both FIP200 and ATG13 are critical for the correct localization of ULK1 to the pre-autophagosome and the stability of ULK1 protein. Additionally, FIP200 and ATG13 can enhance ULK1 kinase activity individually, but both are required for maximal stimulation. The study also shows that ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1·ATG13·FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis. The findings provide insights into the molecular regulation of ULK1 and the integration of autophagy signals in mammalian cells.
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