Proteomic consequences of a human mitochondrial tRNA mutation beyond the frame of mitochondrial translation
Open accessAbstract
Numerous severe neurodegenerative and neuromuscular disorders, characterized biochemically by strong perturbations in energy metabolism, are correlated with single point mutations in mitochondrial genes coding for transfer RNAs. Initial comparative proteomics performed on wild-type and Myoclonic Epilepsy and Ragged Red Fibers (MERRF) mitochondria from sibling human cybrid cell lines revealed the potential of this approach. Here a quantitative analysis of several hundred silver-stained spots separated by two-dimensional gel electrophoresis was performed in the specific case of a couple of mitochondria, containing or not mutation A8344G in the gene for mitochondrial tRNALys, correlated with MERRF syndrome. Computer-assisted analysis allowed us to detect 38 spots with significant quantitative variations, of which 20 could be assigned by mass spectrometry. These include nuclear encoded proteins located in mitochondria such as respiratory chain subunits, metabolic enzymes, a protein of the mitochondrial translation machinery, and cytosolic contaminants. Furthermore, Western blotting combined with mass spectrometry revealed the occurrence of numerous isoforms of pyruvate dehydrogenase subunits, with subtle changes in post-translational modifications. This comparative proteomic approach gives the first insight for nuclear encoded proteins that undergo the largest quantitative changes, and pinpoints new potential molecular partners involved in the cascade of events that connect genotype to phenotype.
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Quantitative analysis of ~800 spots revealed almost 5% with significant quantitative variations in m.8344A N G mutant cybrid cell lines versus control.
“Subsequently, quantitative analysis of N800 total detectable spots revealed almost 5% with significant quantitative variations in m.8344A N G mutant cybrid cell lines versus control [220].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [220]
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Mitochondrial DNA mutations and human disease
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“translation protein, were identified [220].”
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- Authors
- Tryoen-Tóth, P., Richert, S., Sohm, B., Mine, M., Marsac, C., Van Dorsselaer, A., Leize, E., & Florentz, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Florentz, Catherine
- ORCID
- Sohm, Bénédicte
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 278
- Issue
- 27
- Pages
- 24314-24323
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1970602355
- Cited by
- 31
- References
- 57
- Citations by year
- 2022: 1 · 2021: 2 · 2019: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- 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
- MERRF, mitochondrial tRNA mutations, mitochondrial translation, mitochondrial proteome, nuclear-encoded mitochondrial proteins, post-translational modification, genotype-phenotype correlation, energy metabolism disorders
- MeSH terms
- RNA, Mitochondrial, Humans, Mitochondria, Mutation, Nuclear Proteins, RNA, RNA, Transfer, Structure-Activity Relationship, Protein Biosynthesis, Tumor Cells, Cultured, Proteomics
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