title: Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.
abstract: Autophagy is a stress response protecting cells from unfavorable conditions, such as nutrient starvation. The class III phosphatidylinositol-3 kinase, Vps34, forms multiple complexes and regulates both intracellular vesicle trafficking and autophagy induction. Here, we show that AMPK plays a key role in regulating different Vps34 complexes. AMPK inhibits the nonautophagy Vps34 complex by phosphorylating T163/S165 in Vps34 and therefore suppresses overall PI(3)P production and protects cells from starvation. In parallel, AMPK activates the proautophagy Vps34 complex by phosphorylating S91/S94 in Beclin1 to induce autophagy. Atg14L, an autophagy-essential gene present only in the proautophagy Vps34 complex, inhibits Vps34 phosphorylation but increases Beclin1 phosphorylation by AMPK. As such, Atg14L dictates the differential regulation (either inhibition or activation) of different Vps34 complexes in response to glucose starvation. Our study reveals an intricate molecular regulation of Vps34 complexes by AMPK in nutrient stress response and autophagy.
authors: Department of Oral Biochemistry and Molecular Biology, Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea.
authors: Joungmok
authors: J
authors: Kim
authors: Young Chul
authors: YC
authors: Kim
authors: Chong
authors: C
authors: Fang
authors: Ryan C
authors: RC
authors: Russell
authors: Jeong Hee
authors: JH
authors: Kim
authors: Weiliang
authors: W
authors: Fan
authors: Rong
authors: R
authors: Liu
authors: Qing
authors: Q
authors: Zhong
authors: Kun-Liang
authors: KL
authors: Guan
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D058546:Class III Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C561107:Atg14 protein, mouse; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D046912:Multiprotein Complexes; D033921:Vesicular Transport Proteins; D011494:Protein Kinases; D058546:Class III Phosphatidylinositol 3-Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose