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J Biol Chem. 2018 Sep 28;293(39):15021-15032. doi: 10.1074/jbc.RA118.003838. Epub 2018 Aug 7.

Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes.

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From the Department of Neurology, University of Miami School of Medicine, Miami, Florida 33136 and.
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
From the Department of Neurology, University of Miami School of Medicine, Miami, Florida 33136 and


N-Formylation of the Met-tRNAMet 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 MTFMT gene result in Leigh syndrome, a progressive and severe neurometabolic disorder. However, the absolute requirement of formylation of Met-tRNAMet 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-tRNAMet by MTFMT is 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.


N-formylation; gene knockout; methionine; mitochondria; mitochondrial DNA (mtDNA); mitochondrial disease; protein synthesis; transfer RNA (tRNA)

[Available on 2019-09-28]
[Indexed for MEDLINE]

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