Autophagic lysosomal reformation depends on mTOR reactivation in H2O2-induced autophagy

Jiqian Zhang; Wei Zhou; Jun Lin; Pengfei Wei; Yunjiao Zhang; Peipei Jin; Ming Chen; Na Man; Longping Wen

doi:10.1016/j.biocel.2015.11.009

Autophagic lysosomal reformation depends on mTOR reactivation in H2O2-induced autophagy

Int J Biochem Cell Biol. 2016 Jan:70:76-81. doi: 10.1016/j.biocel.2015.11.009. Epub 2015 Nov 14.

Authors

Jiqian Zhang¹, Wei Zhou², Jun Lin¹, Pengfei Wei¹, Yunjiao Zhang¹, Peipei Jin¹, Ming Chen³, Na Man¹, Longping Wen⁴

Affiliations

¹ 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.
² 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: [email protected].
³ 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.
⁴ 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: [email protected].

PMID: 26589722
DOI: 10.1016/j.biocel.2015.11.009

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.

Keywords: Autophagic lysosomal reformation; Autophagy; Hydrogen peroxide; Starvation; mTOR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / drug effects*
Autophagy / genetics
Clathrin / genetics
Clathrin / metabolism
Culture Media / chemistry
Culture Media / pharmacology
Gene Expression Regulation
Genes, Reporter
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
HeLa Cells
Homeostasis / genetics
Humans
Hydrogen Peroxide / pharmacology*
Lysosomes / drug effects*
Lysosomes / metabolism
Lysosomes / ultrastructure
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism
Phagosomes / drug effects*
Phagosomes / metabolism
Phagosomes / ultrastructure
Phosphatidylinositol Phosphates / metabolism
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Signal Transduction
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism*
rab GTP-Binding Proteins / genetics
rab GTP-Binding Proteins / metabolism
rab7 GTP-Binding Proteins

Substances

Clathrin
Culture Media
MAP1LC3A protein, human
Microtubule-Associated Proteins
Phosphatidylinositol Phosphates
Recombinant Fusion Proteins
phosphatidylinositol 4-phosphate
rab7 GTP-Binding Proteins
rab7 GTP-binding proteins, human
Green Fluorescent Proteins
Hydrogen Peroxide
MTOR protein, human
TOR Serine-Threonine Kinases
rab GTP-Binding Proteins