Oliver's mTOR Atlas Evidence Platform
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Pathway link AMPK-ULK1

AMPK ULK1

AMPK activates ULK1.

AMPK also tags ULK1 directly. The long-standing view is that this switches cleanup on; newer work suggests that during a sharp energy crisis AMPK instead holds ULK1 back while protecting it, so the direction is now debated.

AMPK phosphorylates ULK1 at sites distinct from mTORC1's inhibitory S757 site. The classic reading is that low energy therefore switches autophagy on directly, not only by releasing the mTORC1 brake; that reading is now disputed (see boundary).

The conditions it holds under

Contested direction. EGA2010 and KIM2011 report activating phosphorylation. PAR2023 (Park, Lee and Kim, Nat Commun 2023, PMID 37225695) reports that under glucose starvation and mitochondrial energy stress AMPK inhibits ULK1 activation and autophagy induction while protecting the ULK1 machinery from degradation. Which effect dominates appears to depend on the kind and depth of the energy stress.

Time it takes
minutes
Step
direct (one molecule acts on the other)
Measured in
mammalian cells
Where in the cell
cytosol
Reaches people?
plausible in people, not shown directly
How settled
disputed: at least one study points the other way

Studies behind it

YearEvidenceStudy
2010 M Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagyEGA2010 AMPK directly phosphorylates ULK1 to connect energy sensing to autophagy/mitophagy, opposing mTOR.
2011 M AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1KIM2011 Revealed the tug-of-war over ULK1: the energy sensor AMPK phosphorylates ULK1 at activating sites to turn autophagy ON when energy is low, while mTORC1 phosphorylates a different site (Ser757) to keep it OFF and even blocks AMPK from reaching ULK1. Two opposing kinases wired to the same switch.
2016 M A systems study reveals concurrent activation of AMPK and mTOR by amino acidsDAL2016 Adding amino acids back to starved cells switched on AMPK, PI3K and mTORC2 acutely and independently of mTORC1, at the same time as mTOR. AMPK activation ran through CaMKK-beta and, under amino acid sufficiency, AMPK kept autophagy going via ULK1. So the textbook picture of AMPK and mTORC1 as simple opposites does not hold in the first minutes after feeding - which matters for how the AMPK-ULK1 feedback arm behaves over time.

Points the other way

YearEvidenceStudy
2023 M Redefining the role of AMPK in autophagy and the energy stress responsePAR2023 In cultured cells, AMPK activation under glucose starvation or mitochondrial energy stress inhibited ULK1 and autophagy induction, the opposite of the classic activating reading. AMPK also protected the ULK1 machinery from caspase-mediated degradation.

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