AMPK Activates Autophagy by Phosphorylating ULK1

By Kai Mao, D. Klionsky. Circulation Research, 2011

2,477 citations recorded by the source corpus.

### Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy Egan et al Science . 2011;331:456–461. In eukaryotes, macroautophagy (hereafter, autophagy) functions as a highly conserved catabolic mechanism in which cytoplasm, including damaged organelles and protein aggregates, is sequestered into autophagosomes, double-membrane vesicles, for ultimate degradation and recycling in lysosomes. Autophagy has attracted increasing attention in recent years because of its significance in various aspects of cell physiology, including survival during nutrient or energy limitation, and in the clearance of excess or dysfunctional proteins and organelles. In addition, autophagy is associated with a range of human pathophysiologies, including cancer, neurodegeneration, and cardiomyopathies. Autophagy is tightly regulated because either too much or too little can be detrimental to cell physiology. The ULK1 (mammalian homolog of yeast Atg1) kinase complex plays a central role in autophagy induction; the mTORC1 kinase complex, one of the primary negative regulators of autophagy, functions, in part, by phosphorylating and inhibiting ULK1. In contrast, AMPK is a positive regulator that stimulates autophagy in response to energy depletion. Two recent studies suggest that AMPK directly regulates autophagy through phosphorylating and activating ULK1.1,2 mTORC1-dependent phosphorylation appears to work antagonistically to …

Subfields: Epidemiology, Molecular Biology, Physiology

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Citations in the corpus

Autophagy in the Cellular Energetic Balance (2011, neutral): “Activation of a second cellular energy sensor, AMP-activated protein kinase (AMPK), during nutrient deprivation inhibits mTOR activity, reducing ULK1 phosphorylation and promoting its release from mTORC1 (Egan et al., 2011; Kim et al., 2011; Lee et al., 2010b; Shang et al., 2011).”
Cell Death Signaling. (2015, background): “In contrast, AMPK activates the preinitiation complex (Egan et al. 2011; Kim et al. 2011).”
ER stress: Autophagy induction, inhibition and selection (2015, background): “revealed that AMPK induces autophagy by directly phosphorylating ULK1 at 6 different sites (S467, S555, T574, S637, S777, S317).(139,140) In addition, feedback signaling from active AMPK minimizes MTORC1 activation, resulting in an increase in activated ULK1 levels.”
Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β (2011, background): “The principal components of the autophagic signalling and ex- ecution machinery are (i) a protein kinase network including Tor, AMPK, and Ulk1/2 (Egan et al, 2011; Kim et al, 2011), (ii) lipid kinases, principally the class III phosphatidylinositol 3- kinase hVPS34 (Kihara et al, 2001) and potential”
The Role of Autophagy in Cancer: Therapeutic Implications (2011, neutral): “and cell survival during starvation (22).”
Metabolic regulation of hematopoietic stem cells in the hypoxic niche. (2011, background): “Decreased ATP production stimulates AMP-activated protein kinase (AMPK), which increases autophagy not only indirectly through inactivation of mTOR, but also directly through phosphorylation of a mammalian Atg1 homolog, Unc-51-like kinase 1 (Ulk-1) (Egan et al., 2011; Kim et al., 2011).”