ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
- PMID: 23685627
- PMCID: PMC3885611
- DOI: 10.1038/ncb2757
ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
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. Following amino-acid starvation or mTOR inhibition, the activated ULK1 phosphorylates Beclin-1 on Ser 14, thereby enhancing the activity of the ATG14L-containing VPS34 complexes. The Beclin-1 Ser 14 phosphorylation by ULK is required for full autophagic induction in mammals and this requirement is conserved in Caenorhabditis elegans. Our study reveals a molecular link from ULK1 to activation of the autophagy-specific VPS34 complex and autophagy induction.
Conflict of interest statement
The author(s) declare no competing financial interests.
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Comment in
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Autophagy: Kinase crosstalk through beclin 1.Nat Rev Mol Cell Biol. 2013 Jul;14(7):402-3. doi: 10.1038/nrm3608. Epub 2013 Jun 12. Nat Rev Mol Cell Biol. 2013. PMID: 23756621 No abstract available.
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ULK1 targets Beclin-1 in autophagy.Nat Cell Biol. 2013 Jul;15(7):727-8. doi: 10.1038/ncb2797. Nat Cell Biol. 2013. PMID: 23817237 Free PMC article.
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