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

Fingerprint

Peptide Elongation Factor Tu
Peptide Elongation Factors
Leukoencephalopathies
Mitochondrial DNA
Transfer RNA
Mutation
GTP Phosphohydrolases
Mitochondrial Proteins
Protein Biosynthesis
Yeasts
Biopsy
Muscles
Peptides
Genes

Keywords

  • Leukodystrophy
  • Mitochondrial translation
  • OXPHOS defects
  • TUFM

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

@article{d63969c500b74dcfa41d207ed416590e,
title = "Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation",
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.",
keywords = "Leukodystrophy, Mitochondrial translation, OXPHOS defects, TUFM",
author = "{Di Nottia}, Michela and Arianna Montanari and Daniela Verrigni and Romina Oliva and Alessandra Torraco and Erika Fernandez-Vizarra and Daria Diodato and Teresa Rizza and Marzia Bianchi and Michela Catteruccia and Massimo Zeviani and Carlo Dionisi-Vici and Silvia Francisci and Enrico Bertini and Rosalba Carrozzo",
year = "2017",
month = "4",
day = "1",
doi = "10.1016/j.bbadis.2017.01.022",
language = "English",
volume = "1863",
pages = "961--967",
journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation

AU - Di Nottia, Michela

AU - Montanari, Arianna

AU - Verrigni, Daniela

AU - Oliva, Romina

AU - Torraco, Alessandra

AU - Fernandez-Vizarra, Erika

AU - Diodato, Daria

AU - Rizza, Teresa

AU - Bianchi, Marzia

AU - Catteruccia, Michela

AU - Zeviani, Massimo

AU - Dionisi-Vici, Carlo

AU - Francisci, Silvia

AU - Bertini, Enrico

AU - Carrozzo, Rosalba

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - Leukodystrophy

KW - Mitochondrial translation

KW - OXPHOS defects

KW - TUFM

UR - http://www.scopus.com/inward/record.url?scp=85011369436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011369436&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2017.01.022

DO - 10.1016/j.bbadis.2017.01.022

M3 - Article

AN - SCOPUS:85011369436

VL - 1863

SP - 961

EP - 967

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 4

ER -