ULK1.ATG13.FIP200 Complex Mediates MTOR Signaling and is Essential for Autophagy

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Mar 5

PMID 19258318

Citations 771

Authors

Ian G Ganley

Du H Lam

Junru Wang

Xiaojun Ding

She Chen

Xuejun Jiang

Affiliations

Soon will be listed here.

Abstract

Autophagy is a degradative process that recycles long-lived and faulty cellular components. It is linked to many diseases and is required for normal development. ULK1, a mammalian serine/threonine protein kinase, plays a key role in the initial stages of autophagy, though the exact molecular mechanism is unknown. Here we report identification of a novel protein complex containing ULK1 and two additional protein factors, FIP200 and ATG13, all of which are essential for starvation-induced autophagy. Both FIP200 and ATG13 are critical for correct localization of ULK1 to the pre-autophagosome and stability of ULK1 protein. Additionally, we demonstrate by using both cellular experiments and a de novo in vitro reconstituted reaction that FIP200 and ATG13 can enhance ULK1 kinase activity individually but both are required for maximal stimulation. Further, we show 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.

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