Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation

Michela Di Nottia, Arianna Montanari, Daniela Verrigni, Romina Oliva, Alessandra Torraco, Erika Fernandez-Vizarra, Daria Diodato, Teresa Rizza, Marzia Bianchi, Michela Catteruccia, Massimo Zeviani, Carlo Dionisi-Vici, Silvia Francisci, Enrico Bertini, Rosalba Carrozzo

Research output: Contribution to journalArticle

Abstract

The mitochondrial Elongation Factor Tu (EF-Tu), encoded by the TUFM gene, is a highly conserved GTPase, which is part of the mitochondrial protein translation machinery. In its activated form it delivers the aminoacyl-tRNAs to the A site of the mitochondrial ribosome. We report here on a baby girl with severe infantile macrocystic leukodystrophy with micropolygyria and a combined defect of complexes I and IV in muscle biopsy, caused by a novel mutation identified in TUFM. Using human mutant cells and the yeast model, we demonstrate the pathological role of the novel variant. Moreover, results of a molecular modeling study suggest that the mutant is inactive in mitochondrial polypeptide chain elongation, probably as a consequence of its reduced ability to bind mitochondrial aa-tRNAs. Four patients have so far been described with mutations in TUFM, and, following the first description of the disease in a single patient, we describe similar clinical and neuroradiological features in an additional patient.

Original languageEnglish
Pages (from-to)961-967
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1863
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • Leukodystrophy
  • Mitochondrial translation
  • OXPHOS defects
  • TUFM

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation'. Together they form a unique fingerprint.

  • Cite this