Abstract
Autophagy is the primary cellular catabolic program activated in response to nutrient starvation. Initiation of autophagy, particularly by amino acid withdrawal, requires the ULK kinases. Despite its pivotal role in autophagy initiation, little is known about the mechanisms by which ULK promotes autophagy. Here we describe a molecular mechanism linking ULK to the pro-autophagic lipid kinase VPS34. Upon amino acid starvation or mTOR inhibition the activated ULK1 phosphorylates Beclin-1 on S14, thereby, enhancing the activity of the ATG14L-containing VPS34 complexes. The Beclin-1 S14 phosphorylation by ULK is required for full autophagic induction in mammals and this requirement is conserved in C. elegans. Our study reveals a molecular link from ULK1 to activation of the autophagy specific VPS34 complex and autophagy induction.
Accepted Version
Published Version
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