title: Two-layer regulation of PAQR3 on ATG14-linked class III PtdIns3K activation upon glucose starvation.
abstract: As a central node of the macroautophagy/autophagy process, the BECN1/Beclin1-PIK3C3/VPS34 complex participates in different steps of autophagy by interacting with multiple molecules. The ATG14-associated PIK3C3 complex is involved in autophagy initiation, whereas the UVRAG-associated complex mainly modulates autophagosome maturation and endosome fusion. However, the molecular mechanism that coordinates the sequential execution of the autophagy program remains unknown. We have recently discovered that a Golgi-resident protein, PAQR3, regulates autophagy initiation as it preferentially facilitates the formation of the ATG14-linked PIK3C3 complex instead of the UVRAG-associated complex. Upon glucose starvation, AMPK directly phosphorylates T32 of PAQR3, which is crucial for the activation of the ATG14-associated class III PtdIns3K. Furthermore, Paqr3-deleted mice have a deficiency in exercise-induced autophagy as well as behavioral disorders. Thus, this work not only uncovers the regulatory mechanism of PAQR3 on autophagy initiation, but also provides a potential candidate therapeutic target for neurodegenerative diseases.
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences , Shanghai , China.
authors.forename: Daqian
authors.initials: D
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences , Shanghai , China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences , Shanghai , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000172:deficiency*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins; D018345:Mice, Knockout; D008954:Models, Biological; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C561107:Atg14 protein, mouse; D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C523677:RKTG protein, mouse; D033921:Vesicular Transport Proteins; D058546:Class III Phosphatidylinositol 3-Kinases; D005947:Glucose
keywords: AMPK; ATG14; Beclin 1; PAQR3; autophagy; class III PtdIns3K; glucose starvation; nutrient sensing