The R336Q mutation in human mitochondrial EFTu prevents the formation of an active mt-EFTu·GTP·aa-tRNA ternary complex

Lucia Valente, Narumi Shigi, Tsutomu Suzuki, Massimo Zeviani

Research output: Contribution to journalArticle

Abstract

The mitochondrial translational machinery allows the genes encoded by mitochondrial DNA (mtDNA) to be translated in situ. Mitochondrial translation requires a number of nucleus-encoded protein factors, some of which have been found to carry mutations in patients affected by mitochondrial encephalomyopathies. We have previously described the first, and so far only, mutation in the mitochondrial elongation factor Tu, mt-EFTu, in a baby girl with polycystic encephalopathy, micropolygyria, and leukodystrophic changes. Despite that the mutant mt-EFTu was present in normal amount in the patient's tissues, mitochondrial translation was severely reduced, determining multiple defects in the amount and activity of mtDNA-dependent respiratory chain complexes. By an in-vitro reconstructed translational system, we here provide evidence that the mutant mt-EFTu variant fails to bind to aminoacylated mitochondrial tRNAs, thus explaining the observed impairment of mitochondrial translation. This is the first analysis on the molecular mechanism of a mtDNA translation defect due to a nuclear gene mutation.

Original languageEnglish
Pages (from-to)791-795
Number of pages5
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1792
Issue number8
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Mitochondrial translation
  • mt-EFTu binding activity
  • mt-EFTu mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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