Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes
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 neurometa...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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American Society for Biochemistry & Molecular Biology (ASBMB)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125164 |
| _version_ | 1811082229549367296 |
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| author | Arguello, Tania Köhrer, Caroline RajBhandary, Uttam L. Moraes, Carlos T. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Arguello, Tania Köhrer, Caroline RajBhandary, Uttam L. Moraes, Carlos T. |
| author_sort | Arguello, Tania |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:59:46Z |
| format | Article |
| id | mit-1721.1/125164 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:59:46Z |
| publishDate | 2020 |
| publisher | American Society for Biochemistry & Molecular Biology (ASBMB) |
| record_format | dspace |
| spelling | mit-1721.1/1251642022-09-27T23:21:22Z Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes Arguello, Tania Köhrer, Caroline RajBhandary, Uttam L. Moraes, Carlos T. Massachusetts Institute of Technology. Department of Biology 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. National Institutes of Health (Grant 1R01DK090311) 2020-05-11T20:32:21Z 2020-05-11T20:32:21Z 2018-08 2018-08 2020-01-27T20:17:43Z Article http://purl.org/eprint/type/JournalArticle 0021-9258 1083-351X https://hdl.handle.net/1721.1/125164 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 http://dx.doi.org/10.1074/jbc.ra118.003838 Journal of Biological Chemistry Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Society for Biochemistry & Molecular Biology (ASBMB) Other repository |
| spellingShingle | Arguello, Tania Köhrer, Caroline RajBhandary, Uttam L. Moraes, Carlos T. Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| title | Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| title_full | Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| title_fullStr | Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| title_full_unstemmed | Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| title_short | Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| title_sort | mitochondrial methionyl n formylation affects steady state levels of oxidative phosphorylation complexes and their organization into supercomplexes |
| url | https://hdl.handle.net/1721.1/125164 |
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