The association of AMPK with ULK1 regulates autophagy

Jong Woo Lee, Sungman Park, Yoshinori Takahashi, Hong Gang Wang

Research output: Contribution to journalArticle

294 Citations (Scopus)

Abstract

Autophagy is a highly orchestrated intracellular bulk degradation process that is activated by various environmental stresses. The serine/threonine kinase ULK1, like its yeast homologue Atg1, is a key initiator of autophagy that is negatively regulated by the mTOR kinase. However, the molecular mechanism that controls the inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood. Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner. We found that AMPK binds to the PS domain of ULK1 and this interaction is required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex.

Original languageEnglish (US)
Article numbere15394
JournalPloS one
Volume5
Issue number11
DOIs
StatePublished - Nov 18 2010

Fingerprint

AMP-activated protein kinase
AMP-Activated Protein Kinases
autophagy
Autophagy
Raptors
Association reactions
birds of prey
Phosphorylation
phosphorylation
phosphotransferases (kinases)
Protein-Serine-Threonine Kinases
threonine
Yeast
serine
inactivation
Phosphotransferases
Yeasts
Chemical activation
Cells
yeasts

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

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The association of AMPK with ULK1 regulates autophagy. / Lee, Jong Woo; Park, Sungman; Takahashi, Yoshinori; Wang, Hong Gang.

In: PloS one, Vol. 5, No. 11, e15394, 18.11.2010.

Research output: Contribution to journalArticle

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