Zhang Jiqian, Zhou Wei, Lin Jun, Wei Pengfei, Zhang Yunjiao, Jin Peipei, Chen Ming, Man Na, Wen Longping
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.
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.
Int J Biochem Cell Biol. 2016 Jan;70:76-81. doi: 10.1016/j.biocel.2015.11.009. Epub 2015 Nov 14.
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.
自噬性溶酶体重塑是在自噬增强时维持溶酶体稳态的关键细胞过程,迄今为止仅在某些形式的饥饿条件下的细胞中被报道过。因此,这种现象是否具有饥饿特异性以及其在自噬后期溶酶体再生中的重要性一直存在争议。在这里,我们表明外源性过氧化氢(H2O2)诱导了具有自噬性溶酶体重塑特征的溶酶体耗竭和恢复,并且我们通过证明Rab7从自噬溶酶体解离、磷脂酰肌醇4-磷酸(PI4P)和网格蛋白募集到自噬溶酶体表面以及从自噬溶酶体延伸出的管状“前溶酶体”结构的存在,证实了H2O2处理后自噬性溶酶体重塑的发生。与饥饿类似,H2O2导致mTOR最初失活并随后重新激活,并且mTOR重新激活对于自噬性溶酶体重塑至关重要。我们的结果提供了自噬性溶酶体重塑的首个非饥饿实例,并为其在除饥饿之外的某些自噬过程中的重要性提供了证据。