CUL5-SOCS6 complex regulates mTORC2 function by targeting Sin1 for degradation
文献类型：期刊论文
| 作者 | Cui, Binghai1; Gong, Liyan1; Chen, Min1; Zhang, Yuxue1; Gao, Daming1; Yuan, Huairui2; Qin, Jun2; , |
| 刊名 | CELL DISCOVERY
 |
| 出版日期 | 2019 |
| 卷号 | 5期号:-页码:52 |
| 关键词 | Hepatocellular carcinoma Oxidative stress Cardiolipin 4-hydroxy-2-nonenal Apoptosis |
| ISSN号 | 0891-5849 |
| DOI | 10.1038/s41421-019-0118-6 |
| 文献子类 | Letter |
| 英文摘要 | Altered redox status in cancer cells has been linked to lipid peroxidation induced by reactive oxygen species (ROS) and subsequent formation of reactive lipid electrophiles, especially 4-hydroxy-nonenal (4-HNE). Emerging evidence suggests that cancer cells manipulate redox status to acquire anti-apoptotic phenotype but the underlying mechanisms are poorly understood. Cardiolipin (CL), a mitochondria-specific inner membrane phospholipid, is critical for maintaining mitochondrial function. Paradoxically, liver tissues contain tetralinoleoyl cardiolipin (TLCL) as the major CL in mitochondria yet emerging evidence suggests that ROS generated in mitochondria may lead to CL peroxidation and activation of intrinsic apoptosis. It remains unclear how CL oxidation leads to apoptosis and its relevance to the pathogenesis of hepatocellular carcinoma (HCC). We employed a mass spectrometry-based lipidomic approach to profile lipids in human tissues of HCC and found that CL was gradually decreased in tumor comparing to peripheral non-cancerous tissues, accompanied by a concomitant decrease of oxidized CL and its oxidation product, 4-HNE. Incubation of liver cancer cells with TLCL significantly restored apoptotic sensitivity accompanied by an increase of CL and its oxidation products when treated with staurosporine (STS) or Sorafenib (the standard treatment for late stage HCC patients). Our studies uncovered a novel mechanism by which cancer cells adopt to evade apoptosis, highlighting the importance of mitochondrial control of apoptosis through modulation of CL oxidation and subsequent 4-HNE formation in HCC. Thus manipulation of mitochondrial CL oxidation and lipid electrophile formation may have potential therapeutic value for diseases linked to oxidative stress and mitochondrial dysfunctions. |
| 学科主题 | Biochemistry & Molecular Biology ; Endocrinology & Metabolism |
| WOS关键词 | PHOSPHORYLATION ; INTEGRITY |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31798957 |
| WOS记录号 | WOS:000493393500001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1196]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,Innovat Ctr Cell, State Key Lab Cell Biol,CAS Key Lab Syst Biol, Shanghai Inst Biochem & Cell Biol,Chinese Acad Sc, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 2.Univ Chinese Acad Sci, Key Lab Stem Cell Biol,CAS Ctr Excellence Mol Cel, Inst Hlth Sci,Shanghai Inst Biol Sci,Sch Med, Chinese Acad Sci,Shanghai Jiao Tong Univ, Shanghai 200031, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Cui, Binghai,Gong, Liyan,Chen, Min,et al. CUL5-SOCS6 complex regulates mTORC2 function by targeting Sin1 for degradation[J]. CELL DISCOVERY,2019,5(-):52. |
| APA | Cui, Binghai.,Gong, Liyan.,Chen, Min.,Zhang, Yuxue.,Gao, Daming.,...&,.(2019).CUL5-SOCS6 complex regulates mTORC2 function by targeting Sin1 for degradation.CELL DISCOVERY,5(-),52. |
| MLA | Cui, Binghai,et al."CUL5-SOCS6 complex regulates mTORC2 function by targeting Sin1 for degradation".CELL DISCOVERY 5.-(2019):52. |
入库方式： OAI收割
来源：上海营养与健康研究所
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