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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.

Author information

1
From the Department of Neurology, University of Miami School of Medicine, Miami, Florida 33136 and.
2
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
3
From the Department of Neurology, University of Miami School of Medicine, Miami, Florida 33136 and cmoraes@med.miami.edu.

Abstract

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.

KEYWORDS:

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

PMID:
30087118
PMCID:
PMC6166738
[Available on 2019-09-28]
DOI:
10.1074/jbc.RA118.003838
[Indexed for MEDLINE]

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