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Cited by 291

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced autophagy

Open access
Yuan, Hai-Xin, Russell, Ryan C, Guan, Kun-Liang·2013·Autophagy

Abstract

Autophagy is a cellular defense response to stress conditions, such as nutrient starvation. The type III phosphatidylinositol (PtdIns) 3-kinase, whose catalytic subunit is PIK3C3/VPS34, plays a critical role in intracellular membrane trafficking and autophagy induction. PIK3C3 forms multiple complexes and the ATG14-containing PIK3C3 is specifically involved in autophagy induction. Mechanistic target of rapamycin (MTOR) complex 1, MTORC1, is a key cellular nutrient sensor and integrator to stimulate anabolism and inhibit catabolism. Inactivation of TORC1 by nutrient starvation plays a critical role in autophagy induction. In this report we demonstrated that MTORC1 inactivation is critical for the activation of the autophagy-specific (ATG14-containing) PIK3C3 kinase, whereas it has no effect on ATG14-free PIK3C3 complexes. MTORC1 inhibits the PtdIns 3-kinase activity of ATG14-containing PIK3C3 by phosphorylating ATG14, which is required for PIK3C3 inhibition by MTORC1 both in vitro and in vivo. Our data suggest a mechanistic link between amino acid starvation and autophagy induction via the direct activation of the autophagy-specific PIK3C3 kinase.

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Metadata

Authors
Yuan, H.-X., Russell, R. C., & Guan, K.-L.
Venue
Autophagy
Published
2013-12-05
Volume
9
Issue
12
Pages
1983-1995
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
OpenAlex
W2089695512
Cited by
291
References
16
FWCI
11.89
Type
journal article
Language
en
Open access
bronze

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