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

Tania Arguello, Caroline Köhrer, Uttam L. RajBhandary, Carlos T Moraes

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 MTFMTgene 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 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.

Original languageEnglish (US)
Pages (from-to)15021-15032
Number of pages12
JournalJournal of Biological Chemistry
Volume293
Issue number39
DOIs
StatePublished - Jan 1 2018

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RNA, Transfer, Met
Oxidative Phosphorylation
methionyl-tRNA formyltransferase
Methionine
Mitochondria
Leigh Disease
Peptides
Proteins
Mitochondrial Proteins
Mitochondrial DNA
Fibroblasts
Cell Line
Mutation
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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.

In: Journal of Biological Chemistry, Vol. 293, No. 39, 01.01.2018, p. 15021-15032.

Research output: Contribution to journalArticle

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AU - RajBhandary, Uttam L.

AU - Moraes, Carlos T

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