dc.contributor.author | Arguello, Tania | |
dc.contributor.author | Köhrer, Caroline | |
dc.contributor.author | RajBhandary, Uttam L. | |
dc.contributor.author | Moraes, Carlos T. | |
dc.date.accessioned | 2020-05-11T20:32:21Z | |
dc.date.available | 2020-05-11T20:32:21Z | |
dc.date.issued | 2018-08 | |
dc.date.submitted | 2018-08 | |
dc.identifier.issn | 0021-9258 | |
dc.identifier.issn | 1083-351X | |
dc.identifier.uri | https://hdl.handle.net/1721.1/125164 | |
dc.description.abstract | N-Formylation of the Met-tRNA Met by the nuclearly encoded mitochondrial methionyl-tRNA formyltransferase (MTFMT) has been found to be a key determinant of protein synthesis initiation in mitochondria. In humans, mutations in the MTFMTgene result in Leigh syndrome, a progressive and severe neurometabolic disorder. However, the absolute requirement of formylation of Met-tRNA Met for protein synthesis in mammalian mitochondria is still debated. Here, we generated a Mtfmt-KO mouse fibroblast cell line and demonstrated that N-formylation of the first methionine via fMet-tRNA Met by MTFMTis not an absolute requirement for initiation of protein synthesis. However, it differentially affected the efficiency of synthesis of mtDNA-coded polypeptides. Lack of methionine N-formylation did not compromise the stability of these individual subunits but had a marked effect on the assembly and stability of the OXPHOS complexes I and IV and on their supercomplexes. In summary, N-formylation is not essential for mitochondrial protein synthesis but is critical for efficient synthesis of several mitochondrially encoded peptides and for OXPHOS complex stability and assembly into supercomplexes. | en_US |
dc.description.sponsorship | National Institutes of Health (Grant 1R01DK090311) | en_US |
dc.language.iso | en | |
dc.publisher | American Society for Biochemistry & Molecular Biology (ASBMB) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1074/jbc.ra118.003838 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | Other repository | en_US |
dc.title | Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Arguello, Tania et al. "Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes." Journal of Biological Chemistry 293, 39 (August 2018): 15021-15032. © 2018 Arguello et al. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.relation.journal | Journal of Biological Chemistry | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2020-01-27T20:17:43Z | |
dspace.date.submission | 2020-01-27T20:17:46Z | |
mit.journal.volume | 293 | en_US |
mit.journal.issue | 39 | en_US |
mit.metadata.status | Complete | |