个人中心| | 帮助
高级检索
当前位置： 首页 > 详情页

NADP(+)-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance.

| 认领 | 导出 | |

文献详情

资源类型：
WOS体系：
Pubmed体系：

收录情况： ◇ SCIE ◇ 自然指数

作者：
Feng Li[1,2,8] ; Xiadi He[1,3,8] ; Dingwei Ye[4,5] ; Yan Lin[1,2,8] ; Hongxiu Yu[2] ; Cuifang Yao[1,2] ; Lei Huang[1,3] ; Jianong Zhang[1,3] ; Fang Wang[2] ; Sha Xu[1,2] ; Xiaohui Wu[1,7] ; Lixia Liu[9] ; Chen Yang[9] ; Jiaqi Shi[10] ; Xiaoyang He[11] ; Jie Liu[2,6,10] ; Yuanyuan Qu[4,5] ; Fushen Guo[1,2,3] ; Jianyuan Zhao[1,3] ; Wei Xu[1,2,8] ; Shimin Zhao[1,2,3,6,8] ;
机构： [1]State Key Lab of Genetic Engineering and the Obstetrics & Gynecology Hospital of Fudan University [2]Institutes of Biomedical Sciences,Fudan University, Shanghai 200032, P.R. China [3]School of Life Sciences and Collaborative Innovation Center for Genetics and Development,Fudan University, Shanghai 200032, P.R. China [4]Department of Urology, Fudan University Shanghai Cancer Center,Fudan University, Shanghai 200032, P.R. China [5]Department of Oncology, Shanghai Medical College,Fudan University, Shanghai 200032, P.R. China [6]Institute of Digestive Medicine, Affiliated Huashan Hospital,Fudan University, Shanghai 200032, P.R. China [7]Institute of Developmental Biology and Molecular Medicine,Fudan University, Shanghai 200032, P.R. China [8]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P.R. China [9]Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China [10]Department of Urology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, P.R. China [11]Guizhou Cancer Hospital, Guiyang 550001, P.R. China
出处：
DOI： 10.1016/j.molcel.2015.10.017
ISSN：

摘要：
Elucidating the tumorigenic mechanism of R-2-hydroxyglutarate (R-2HG) is critical for determining how NADP(+)-IDH mutations cause cancer. Here we report that R-2HG induces cancerous metabolism and apoptosis resistance through promoting hypersuccinylation. By competitive inhibition of the mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH), R-2HG preferentially induced succinyl-CoA accumulation and hypersuccinylation in the mitochondria. IDH1 mutation-bearing glioma samples and cells were hypersuccinylated in the mitochondria. IDH1 mutation or SDH inactivation resulted in hypersuccinylation, causing respiration inhibition and inducing cancerous metabolism and mitochondrial depolarization. These mitochondrial dysfunctions induced BCL-2 accumulation at the mitochondrial membrane, leading to apoptosis resistance of hypersuccinylated cells. Relief of hypersuccinylation by overexpressing the desuccinylase SIRT5 or supplementing glycine rescued mitochondrial dysfunctions, reversed BCL-2 accumulation, and slowed the oncogenic growth of hypersuccinylated IDH1(R132C)-harboring HT1080 cells. Thus, R-2HG-induced hypersuccinylation contributes to the tumorigenicity of NADP(+)-IDH mutations, suggesting the potential of hypersuccinylation inhibition as an intervention for hypersuccinylation-related tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

基金：
This work was supported by the State Key Development Programs (973) of Basic Research of China (numbers 2012CB910103, 2013CB531200, 2013CB945401, 2013CB911204, 2015CB943300, and 2015AA020913), grants from the National Science Foundation of China (numbers 31330023, 81301717, and 81471454), International Cooperative grant from Minister of Science and Technology (2014DFA30630), and Science and Technology Municipal Commission of Shanghai (numbers 12ZR1440800 and 14ZR1402000).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类 | 1 区 生物
小类 | 1 区 生化与分子生物学 1 区 细胞生物学
最新[2023]版：
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学 1 区 细胞生物学
JCR分区：
出版当年[2015]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

第一作者：
第一作者机构： [1]State Key Lab of Genetic Engineering and the Obstetrics & Gynecology Hospital of Fudan University [2]Institutes of Biomedical Sciences,Fudan University, Shanghai 200032, P.R. China [8]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P.R. China
共同第一作者：
通讯作者：
通讯机构： [1]State Key Lab of Genetic Engineering and the Obstetrics & Gynecology Hospital of Fudan University [2]Institutes of Biomedical Sciences,Fudan University, Shanghai 200032, P.R. China [3]School of Life Sciences and Collaborative Innovation Center for Genetics and Development,Fudan University, Shanghai 200032, P.R. China [6]Institute of Digestive Medicine, Affiliated Huashan Hospital,Fudan University, Shanghai 200032, P.R. China [8]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P.R. China
推荐引用方式(GB/T 7714)：
Feng Li,Xiadi He,Dingwei Ye,et al.NADP(+)-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance.[J].MOLECULAR CELL.2015,60(4):661-675.doi:10.1016/j.molcel.2015.10.017.
APA：
Feng Li,Xiadi He,Dingwei Ye,Yan Lin,Hongxiu Yu...&Shimin Zhao.(2015).NADP(+)-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance..MOLECULAR CELL,60,(4)
MLA：
Feng Li,et al."NADP(+)-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance.".MOLECULAR CELL 60..4(2015):661-675

资源点击量：43389 今日访问量：0 总访问量：3120 更新日期：2024-09-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 四川省肿瘤医院 技术支持：重庆聚合科技有限公司 地址：成都市人民南路四段55号