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Cited by 55Mitochondrial Function and PathologyAdvanced Proteomics Techniques and ApplicationsMetabolism and Genetic Disorders

Comparative proteomics as a new tool for exploring human mitochondrial tRNA disorders

Rabilloud, Thierry, Strub, Jean-Marc, Carte, Nathalie, Luche, Sylvie, Van Dorsselaer, Alain, Lunardi, Joël, Giegé, Richard, Florentz, Catherine·2002·Biochemistry
DOI 10.1021/bi0114776
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Abstract

More than 70 different point mutations in human mitochondrial tRNA genes are correlated with severe disorders, including fatal cardiopathies, encephalopathies, myopathies, and others. So far, investigation of the molecular impact(s) of mutations has focused on the affected tRNA itself by seeking structural and/or functional perturbations capable of interfering with synthesis of the 13 mitochondrion-encoded subunits of respiratory chain complexes. Here, a proteomic approach was used to investigate whether such mutations would affect the pattern of mitochondrial proteins at a broader level. Analysis of several hundred mitochondrial proteins from sibling cybrid cell lines by two-dimensional electrophoresis, an approach that takes into account all regulatory steps of mitochondrial and nuclear gene expression, indeed reveals a number of up- and downregulated proteins when healthy and single-point-mutation-carrying mitochondria representative of either MELAS or MERRF syndrome were compared. Assignment by mass spectrometry of the two proteins which exhibit obvious large quantitative decreases in the levels of both pathologic mitochondria identified nuclear-encoded subunits of cytochrome c oxidase, a respiratory chain complex. This clearly shows a linkage between the effects of mutations in mitochondrial tRNA genes and the steady-state level of nuclear-encoded proteins in mitochondria. It opens new routes toward a large-scale exploration of potential proteic partners involved in the genotype-phenotype correlation of mitochondrial disorders.

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  • Expression levels of nuclear-encoded CIV subunits Vb and VIa were dramatically reduced in both m.8344A N G and m.3243A N G mutant cybrid cell lines relative to wild-type.

    “In particular, the expression levels of two proteins, both nuclear-encoded subunits of CIV (Vb and VIa), were shown to be dramatically reduced in both mutant cell lines relative to their sibling wild-type.”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [219]

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Authors
Rabilloud, T., Strub, J.-M., Carte, N., Luche, S., Van Dorsselaer, A., Lunardi, J., Giegé, R., & Florentz, C.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Institut de Biologie Moléculaire et Cellulaire, UPR 9002 du CNRS, 15, rue René Descartes, F-67084 Strasbourg Cedex, France, CEA-Laboratoire de Bioénergétique Cellulaire et Pathologique, UA 2019 DBMS/BECP, 17, rue des Martyrs, F-38054 Grenoble Cedex 9, France, and Laboratoire de Spectrométrie de Masse Bio-organique, UMR 7509 ULP-CNRS, Ecole de Chimie Polymères et Matériaux, 25 rue Bequerel, F-67087 Strasbourg Cedex 2, France
ORCID
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2001-12-07
Volume
41
Issue
1
Pages
144-150
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/bi0114776
OpenAlex
W2080211953
Cited by
55
References
19
Citations by year
2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2016: 2 · 2014: 5 · 2013: 1 · 2012: 3
FWCI
2.08
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion)
Funders
California Institute of Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
mitochondrial tRNA mutations, mitochondrial disease, MELAS, MERRF syndrome, cytochrome c oxidase, nuclear-encoded mitochondrial proteins, mitochondrial proteome, electron transport chain, genotype-phenotype correlation, protein expression regulation
MeSH terms
RNA, Mitochondrial, Amino Acid Sequence, Cell Line, Cell Nucleus, DNA, Mitochondrial, Humans, Mitochondria, Molecular Sequence Data, RNA, RNA, Transfer, Electrophoresis, Gel, Two-Dimensional, Point Mutation, Proteome, Mitochondrial Proteins, Genetic Diseases, Inborn

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