title: PAQR3 augments amino acid deprivation-induced autophagy by inhibiting mTORC1 signaling.
abstract: Amino acids are the key activators of the mTOR complex 1 (mTORC1, mainly composed of mTOR, Raptor and mLST8) required for cell growth and proliferation. On the other hand, deprivation of amino acids induces autophagy via inhibition of mTORC1 signaling. We report here that amino acid-induced mTORC1 activity and amino acid deprivation-induced autophagy are regulated by PAQR3, a newly found tumor suppressor. At the cellular level, PAQR3 negatively regulates amino acid-induced activation of mTORC1. The N-terminal end of PAQR3 interacts with the WD domains of Raptor and mLST8 directly. PAQR3 reduces the interaction of mTOR with Raptor and mLST8, thus disrupts formation of intact mTORC1 complex. PAQR3 modulates leucine-induced alteration in cell size. In addition, PAQR3 knockdown reduces amino acid deprivation-induced autophagy. The inhibitory effect of PAQR3 knockdown on autophagy is abrogated by rapamycin treatment, indicating that PAQR3 modulates autophagy via its regulation on mTORC1 signaling. In conclusion, our finding reveals a new mode of regulation of mTORC1 signaling and autophagy by PAQR3 in response to alterations of amino acids.
authors.affiliation: CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Huang
authors.affiliation: CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Sciences and Technology, Shanghai Tech University, Shanghai 200031, China.
authors.forename: Xue
authors.initials: X
authors.lastname: You
authors.affiliation: CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
authors.affiliation: CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Sciences and Technology, Shanghai Tech University, Shanghai 200031, China. Electronic address: ychen3@sibs.ac.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism / Q000648:ultrastructure; D001343:Autophagy; D002460:Cell Line; D048429:Cell Size; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D000076223:Regulatory-Associated Protein of mTOR / Q000378:metabolism; D015398:Signal Transduction; D000076242:mTOR Associated Protein, LST8 Homolog / Q000378:metabolism
chemical_list: D000596:Amino Acids; D047908:Intracellular Signaling Peptides and Proteins; C555285:MLST8 protein, human; D008565:Membrane Proteins; C532354:PAQR3 protein, human; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D000076242:mTOR Associated Protein, LST8 Homolog; D000076222:Mechanistic Target of Rapamycin Complex 1
keywords: Autophagy; Nutrient sensing; PAQR3; mTOR; mTORC1