Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells.
Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells.
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DOI：
10.1038/s41598-017-12485-2
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发表时间：
2017-09-26
影响因子：
4.6
通讯作者：
Yin XM
中科院分区：
文献类型：
--
作者：
Wang L;Zhou J;Yan S;Lei G;Lee CH;Yin XM
乙醇诱导的肝细胞吞噬脂肪功能对肝损伤具有重要的细胞保护作用，但其机制尚未完全确定。在本研究中，乙醇诱导的脂肪吞噬研究在永生化小鼠肝细胞系，AML 12。我们发现，乙醇处理增加了这些细胞中的脂质含量，这可以通过自噬来调节。为了确定潜在的机制，我们研究了关键衔接分子SQSTM 1/p62的作用。SQSTM 1可以与自噬体上的LC 3和货物上的泛素化分子结合，从而促进货物的自噬吞噬。我们发现LC 3和SQSTM 1都可以与乙醇处理后的脂滴（LD）共定位。SQSTM 1敲低显著抑制了LC 3与LD的共定位，这也降低了乙醇诱导的脂质升高。此外，增加的泛素信号被发现与响应于乙醇的LD上的SQSTM 1共定位。此外，SQSTM 1信号与LD上的主要蛋白perilipin 1信号共定位。最后，perilipin 1敲低显着改变乙醇诱导的脂肪吞噬。总之，这些数据支持一种模型，其中自噬体通过SQSTM 1被定向到LD，SQSTM 1结合到LD上的泛素化蛋白，可能包括围脂蛋白1。本研究为乙醇诱导肝细胞吞噬脂肪的机制提供了一个可能的解释。
Ethanol-induced hepatic lipophagy plays an important cytoprotective role against liver injury, but its mechanism is not fully determined. In the present study, ethanol-induced lipophagy was studied in an immortalized mouse hepatocyte line, AML12. We found that ethanol treatment elevated lipid content in these cells, which could be regulated by autophagy. To determine the potential mechanism, we investigated the role of a key adaptor molecule SQSTM1/p62. SQSTM1 can bind to LC3 on autophagosomes and ubiquitinated molecules on cargos, thus facilitating the autophagic engulfment of the cargo. We found that both LC3 and SQSTM1 could colocalize with lipid droplets (LDs) following ethanol treatment. Colocalization of LC3 with LDs was significantly inhibited by SQSTM1 knockdown, which also reduced ethanol-induced lipid elevation. In addition, increased ubiquitin signals were found to colocalize with SQSTM1 on LDs in response to ethanol. Moreover, the SQSTM1 signal was colocalized with that of perilipin1, a major protein on LDs. Finally, perilipin1 knockdown significantly altered ethanol-induced lipophagy. Taken together, these data support a model in which autophagosomes were directed to the LDs via SQSTM1, which bound to ubiquitinated proteins, possibly including perilipin 1, on LDs. This study provides a potential mechanistic explanation to how ethanol induces lipophagy in hepatocytes.
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影响因子：
2.3
作者：
Fujimoto, Toyoshi;Ohsaki, Yuki;Cheng, Jinglei;Suzuki, Michitaka;Shinohara, Yuki
通讯作者：
Shinohara, Yuki
影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
4.8
作者：
Petiot, A;Ogier-Denis, E;Codogno, P
通讯作者：
Codogno, P
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
21.3
作者：
Komatsu, Masaaki;Kurokawa, Hirofumi;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki