title: Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy.
abstract: Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes. Canonical autophagy requires all autophagy proteins (ATGs), whereas noncanonical autophagy is activated by diverse agents in which some of the essential autophagy proteins are dispensable. How noncanonical autophagy is induced and/or inhibited is still largely unclear. In this study, we demonstrated that AMDE-1, a recently identified chemical that can induce canonical autophagy, was able to elicit noncanonical autophagy that is independent of the ULK1 (unc-51-like kinase 1) complex and the Beclin1 complex. AMDE-1-induced noncanonical autophagy could be specifically suppressed by various V-ATPase (vacuolar-type H(+)-ATPase) inhibitors, but not by disturbance of the lysosome function or the intracellular ion redistribution. Similar findings were applicable to a diverse group of stimuli that can induce noncanonical autophagy in a FIP200-independent manner. AMDE-1-induced LC3 lipidation was colocalized with the Golgi complex, and was inhibited by the disturbance of Golgi complex. The integrity of the Golgi complex was also required for multiple other agents to stimulate noncanonical LC3 lipidation. These results suggest that the Golgi complex may serve as a membrane platform for noncanonical autophagy where V-ATPase is a key player. V-ATPase inhibitors could be useful tools for studying noncanonical autophagy.
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Ying
authors: Y
authors: Gao
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Yajun
authors: Y
authors: Liu
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Liang
authors: L
authors: Hong
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Zuolong
authors: Z
authors: Yang
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Xinran
authors: X
authors: Cai
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Xiaoyun
authors: X
authors: Chen
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Yuanyuan
authors: Y
authors: Fu
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Yujie
authors: Y
authors: Lin
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Weijie
authors: W
authors: Wen
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Sitong
authors: S
authors: Li
authors: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Xingguo
authors: X
authors: Liu
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Heqing
authors: H
authors: Huang
authors: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors: Andreas
authors: A
authors: Vogt
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Peiqing
authors: P
authors: Liu
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Xiao-Ming
authors: XM
authors: Yin
authors: National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors: Min
authors: M
authors: Li
mesh_terms: D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism; D000071186:Beclin-1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007476:Ionophores / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D025801:Ubiquitin / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D000071186:Beclin-1; C115010:Becn1 protein, mouse; D004791:Enzyme Inhibitors; D007476:Ionophores; D008055:Lipids; D018942:Macrolides; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D025801:Ubiquitin; C040929:bafilomycin A1; D000071189:Autophagy-Related Protein-1 Homolog; C112444:Ulk1 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases