期刊
MOLECULAR CELL
卷 67, 期 6, 页码 922-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.08.013
关键词
-
资金
- Canadian Institutes of Health Research [CIHR MOP-7214, FDN-148423, MOP-5605, MOP-68833, MOP-115195, PJT-148603, MOP-106603]
- Canadian Cancer Society Research Institute [CCSRI 16208]
- Terry Fox Research Institute [TFF-116128, TFF-242122]
- National Sciences and Engineering Research Council of Canada
- CIHR New Investigator Salary
- Canadian Diabetes Association postdoctoral fellowship
- CIHR postdoctoral fellowship [MFE-140925]
- CIHR Vanier Canada Graduate Scholarship [VGS-338305]
- Swedish Research Council
- Swedish Cancer Society
- Wallenberg Academy Fellow program
The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission/fusion, ATP production, metabolite biogenesis, and apoptosis, are not well understood. Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase dynamin-related protein 1 (DRP1). Potent active-site mTOR inhibitors engender mitochondrial hyperfusion due to the diminished translation of MTFP1, which is mediated by translation initiation factor 4E (eIF4E)binding proteins (4E-BPs). Uncoupling MTFP1 levels from them TORC1/4E-BP pathway up on mTOR inhibition blocks the hyperfusion response and leads to apoptosis by converting mTOR inhibitor action from cytostatic to cytotoxic. These data provide direct evidence for cell survival upon mTOR inhibition through mitochondrial hyperfusion employing MTFP1as a critical effector of mTORC1 to govern cell fate decisions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据