Regulation of the autophagy initiating kinase ULK1 by nutrients: roles of mTORC1 and AMPK

Abstract

The serine/threonine kinase ULK1 is a mammalian homolog of AT G1, an upstream component of the core autophagy machinery. Studies in yeast AT G1 kinase complex demonstrate that the AT G1 kinase complex assembly is regulated by phosphorylaltion of AT G13 in a TORC1-dependent manner. However, the mammalian ULK1 complex appears to have different mechanisms of regulation because the mammalian ULK1-AT G13 association is not regulated by TORC1. Recently, we and Shaw’s group reported that AMPK phosphorylates ULK1 in response to cellular energy starvation to control ULK1 kinase function and autophagy induction. When nutrients are sufficient, mTORC1 phosphorylates ULK1, preventing its association and activation by AMPK. These studies have revealed a molecular mechanism of ULK1 regulation by nutrient signals via the coordinated actions of AMPK and mTORC1.