title: Deacetylation of nuclear LC3 drives autophagy initiation under starvation.
abstract: Shuttling of macromolecules between different cellular compartments helps regulate the timing and extent of different cellular activities. Here, we report that LC3, a key initiator of autophagy that cycles between the nucleus and cytoplasm, becomes selectively activated in the nucleus during starvation through deacetylation by the nuclear deacetylase Sirt1. Deacetylation of LC3 at K49 and K51 by Sirt1 allows LC3 to interact with the nuclear protein DOR and return to the cytoplasm with DOR, where it is able to bind Atg7 and other autophagy factors and undergo phosphatidylethanolamine conjugation to preautophagic membranes. The association of deacetylated LC3 with autophagic factors shifts LC3's distribution from the nucleus toward the cytoplasm. Thus, an acetylation-deacetylation cycle ensures that LC3 effectively redistributes in an activated form from nucleus to cytoplasm, where it plays a central role in autophagy to enable the cell to cope with the lack of external nutrients.
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shou
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lippincott-Schwartz
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address: liuwei666@zju.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D056564:Sirtuin 1 / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D008239:Lysine