mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1

作者：Morita Masahiro; Prudent Julien; Basu Kaustuv; Goyon Vanessa; Katsumura Sakie; Hulea Laura; Pearl Dana; Siddiqui Nadeem; Strack Stefan; McGuirk Shawn; St Pierre Julie; Larsson Ola; Topisirovic Ivan; Vali Hojatollah; McBride Heidi M; Bergeron John J; Sonenberg Nahum

来源：Molecular Cell, 2017, 67(6): 922-+.

DOI：10.1016/j.molcel.2017.08.013

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.

• 出版日期2017-9-21