title: Formation of a Snf1-Mec1-Atg1 Module on Mitochondria Governs Energy Deprivation-Induced Autophagy by Regulating Mitochondrial Respiration.
abstract: Autophagy is essential for maintaining glucose homeostasis, but the mechanism by which energy deprivation activates autophagy is not fully understood. We show that Mec1/ATR, a member of the DNA damage response pathway, is essential for glucose starvation-induced autophagy. Mec1, Atg13, Atg1, and the energy-sensing kinase Snf1 are recruited to mitochondria shortly after glucose starvation. Mec1 is recruited through the adaptor protein Ggc1. Snf1 phosphorylates Mec1 on the mitochondrial surface, leading to recruitment of Atg1 to mitochondria. Furthermore, the Snf1-mediated Mec1 phosphorylation and mitochondrial recruitment of Atg1 are essential for maintaining mitochondrial respiration during glucose starvation, and active mitochondrial respiration is required for energy deprivation-activated autophagy. Thus, formation of a Snf1-Mec1-Atg1 module on mitochondria governs energy deprivation-induced autophagy by regulating mitochondrial respiration.
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Yi
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tong
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Puzhong
authors.initials: P
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jinxie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Membrane Biology, School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Kangning
authors.initials: K
authors.lastname: Yuan
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Renyu
authors.initials: R
authors.lastname: Xue
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zou
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Nianzhong
authors.initials: N
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xiao
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Dai
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Proteomics Centre, National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Proteomics Centre, National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: Proteomics Facility, School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Di
authors.initials: D
authors.lastname: Miao
authors.affiliation: Proteomics Facility, School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Haiteng
authors.initials: H
authors.lastname: Deng
authors.affiliation: Cardiovascular Research Institute of Wuhan University, JieFang Road 238, Wuhan 430060, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: liyulab@mail.tsinghua.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D019069:Cell Respiration / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C413216:ATG13 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; C071570:SNF1-related protein kinases; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D005947:Glucose
keywords: Mec1/ATR; Snf1/Mec1/Atg1; autophagy; energy deprivation; mitochondria; mitochondria respiration