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

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• 作者：Jiqian Zhang^a ; ^b ; Wei Zhou^a ; ^b ; ^{zhouweid@ustc.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Jun Lin^a ; ^b ; Pengfei Wei^a ; ^b ; Yunjiao Zhang^a ; ^b ; Peipei Jin^a ; ^b ; Ming Chen^a ; ^c ; ^d ; Na Man^a ; ^b ; Longping Wen^a ; ^b ; ^{lpwen@ustc.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ALR ; autophagic lysosomal reformation ; H2O2 ; hydrogen peroxide ; Rab7 ; Ras-related protein 7 ; PI4P ; phosphatidylinositol 4-phosphate ; mTOR ; mammalian mechanistic target of rapamycin ; Atg ; autophagy-related gene ; DMEM ; Dulbecco's Modified Eagle's Medium ; EBSS ; Earle's Balanced Salts Solution ; HBSS ; Hank's buffered salt solution ; PI(4 ; 5)P2 ; PI4phosphatidylinositol 4 ; 5-bisphosphate ; PIP5K ; phosphatidylinositol 4-phosphate 5-kinase
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：70
• 期：Complete
• 页码：76-81
• 全文大小：1648 K

文摘

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.