title: Autophagic lysosomal reformation depends on mTOR reactivation in H2O2-induced autophagy.
abstract: Autophagic lysosomal reformation, a key cellular process for maintaining lysosome homeostasis in elevated autophagy, so far has only been reported for cells under certain forms of starvation. For this reason, it is controversial that whether this phenomenon is starvation-specific and its importance in lysosomal regeneration at the late stage of autophagy is often challenged. Here we show that exogenous hydrogen peroxide (H2O2) induced lysosome depletion and recovery characteristic of autophagic lysosomal reformation, and we confirmed the occurrence of autophagic lysosomal reformation after H2O2 treatment by demonstrating Rab7 dissociation from autolysosomes, recruitment of Phosphatidylinositol 4-phosphate (PI4P) and clathrin to the surface of autolysosomes, and the existence of tubular "pro-lysosome" structures extending from autolysosomes. Similar to starvation, H2O2 caused an initial deactivation and a subsequent reactivation for mTOR, and mTOR reactivation was essential for ALR. Our results provided a first non-starvation example of autophagic lysosomal reformation and provide evidence for its importance for some autophagic processes other than that of starvation.
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Jiqian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China. Electronic address: zhouweid@ustc.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wei
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Jin
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Department of Pharmacology, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China; Anhui Anke Biotechnology (Group) Co., Ltd., Hefei, Anhui, 230088, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Na
authors.initials: N
authors.lastname: Man
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China. Electronic address: lpwen@ustc.edu.cn.
authors.forename: Longping
authors.initials: L
authors.lastname: Wen
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D002966:Clathrin; D003470:Culture Media; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D018129:Phosphatidylinositol Phosphates; D011993:Recombinant Fusion Proteins; C037178:phosphatidylinositol 4-phosphate; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D049452:Green Fluorescent Proteins; D006861:Hydrogen Peroxide; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020691:rab GTP-Binding Proteins
keywords: Autophagic lysosomal reformation; Autophagy; Hydrogen peroxide; Starvation; mTOR