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dc.contributor.authorMorita, Men
dc.contributor.authorPrudent, Julienen
dc.contributor.authorBasu, Ken
dc.contributor.authorGoyon, Ven
dc.contributor.authorKatsumura, Sen
dc.contributor.authorHulea, Len
dc.contributor.authorPearl, Den
dc.contributor.authorSiddiqui, Nen
dc.contributor.authorStrack, Sen
dc.contributor.authorMcGuirk, Sen
dc.contributor.authorSt-Pierre, Jen
dc.contributor.authorLarsson, Oen
dc.contributor.authorTopisirovic, Ien
dc.contributor.authorVali, Hen
dc.contributor.authorMcBride, HMen
dc.contributor.authorBergeron, Jen
dc.contributor.authorSonenberg, Nen
dc.date.accessioned2017-10-09T12:38:21Z
dc.date.available2017-10-09T12:38:21Z
dc.date.issued2017-09-21en
dc.identifier.issn1097-2765
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/267802
dc.description.abstractThe mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission and 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) protein 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 mediated by the translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). Uncoupling MTFP1 levels from the mTORC1/4EBP pathway upon 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 the survival function of mitochondrial hyperfusion upon mTOR inhibition by employing MTFP1 as a critical effector of mTORC1 to govern cell fate decisions.
dc.language.isoenen
dc.publisherElsevier
dc.titlemTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1en
dc.typeArticle
prism.endingPage935.e5
prism.issueIdentifier6en
prism.publicationDate2017en
prism.publicationNameMolecular Cellen
prism.startingPage922
prism.volume67en
dc.identifier.doi10.17863/CAM.12998
dcterms.dateAccepted2017-08-18en
rioxxterms.versionofrecord10.1016/j.molcel.2017.08.013en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-09-21en
dc.contributor.orcidPrudent, Julien [0000-0003-3821-6088]
dc.identifier.eissn1097-4164
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_00015/7)
cam.issuedOnline2017-09-14en
datacite.issupplementedby.doi10.17632/mjfjdvvw75.1en
rioxxterms.freetoread.startdate2018-09-21


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