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Cited by 157Mitochondrial Function and PathologyRNA and protein synthesis mechanismsRNA modifications and cancer

The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.

Nuclear DNA-encoded tRNAs targeted into mitochondria can rescue a mitochondrial DNA mutation associated with the MERRF syndrome in cultured human cells

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Kolesnikova, Olga A., Entelis, Nina S., Jacquin-Becker, Clarisse, Goltzene, Francine, Chrzanowska-Lightowlers, Zofia M., Lightowlers, Robert N., Martin, Robert P., Tarassov, Ivan·2004·Human Molecular Genetics
DOI 10.1093/hmg/ddh267
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Abstract

Mitochondrial DNA (mtDNA) mutations are an important cause of human disease for which there is no efficient treatment. Our aim was to determine whether the A8344G mitochondrial tRNA(Lys) mutation, which can cause the MERRF (myoclonic epilepsy with ragged-red fibers) syndrome, could be complemented by targeting tRNAs into mitochondria from the cytosol. Import of small RNAs into mitochondria has been demonstrated in many organisms, including protozoans, plants, fungi and animals. Although human mitochondria do not import tRNAs in vivo, we previously demonstrated that some yeast tRNA derivatives can be imported into isolated human mitochondria. We show here that yeast tRNALys derivatives expressed in immortalized human cells and in primary human fibroblasts are partially imported into mitochondria. Imported tRNAs are correctly aminoacylated and are able to participate in mitochondrial translation. In transmitochondrial cybrid cells and in patient-derived fibroblasts bearing the MERRF mutation, import of tRNALys is accompanied by a partial rescue of mitochondrial functions affected by the mutation such as mitochondrial translation, activity of respiratory complexes, electrochemical potential across the mitochondrial membrane and respiration rate. Import of a tRNALys with a mutation in the anticodon preventing recognition of the lysine codons does not lead to any rescue, whereas downregulation of the transgenic tRNAs by small interfering RNA (siRNA) transiently abolishes the functional rescue, showing that this rescue is due to the import. These findings prove for the first time the functionality of imported tRNAs in human mitochondria in vivo and highlight the potential for exploiting the RNA import pathway to treat patients with mtDNA diseases.

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Crossref · 10.1093/hmg/ddh267

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67 of 67 references verified0 citation errors · 0 not checkable

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  • Yeast tRNA Lys derivatives can be expressed and imported into mitochondria in cybrid cells and primary human fibroblasts with m.8344A N G MERRF mutation.

    “For mt-tRNA mutations, yeast tRNA Lys derivatives can be expressed and imported into mitochondria within cybrid cells and primary human fibroblasts harbouring the m.8344A N G MERRF mutation.”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [242]

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Research works printed but not linked: 1

  1. Entelis, N.S., Kieffer, S., Kolesnikova, O.A., Martin, R.P. and Tarassov, I.A. (1998) Structural requirements of tRNALys for its import into yeast mitochondria. Proc. Natl Acad. Sci. USA, 95, 2838–2843. · DOI

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Metadata

Authors
Kolesnikova, O. A., Entelis, N. S., Jacquin-Becker, C., Goltzene, F., Chrzanowska-Lightowlers, Z. M., Lightowlers, R. N., Martin, R. P., & Tarassov, I.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Génétique Moléculaire Génomique Microbiologie (FR)
  • Wellcome Centre for Mitochondrial Research (GB)
Corresponding author
Kolesnikova, Olga A.
ORCID
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2004-08-18
Volume
13
Issue
20
Pages
2519-2534
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/ddh267
OpenAlex
W2158316645
Cited by
157
References
67
Citations by year
2026: 2 · 2025: 7 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 11
FWCI
2.96
Type
journal article
Language
en
Open access
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
MERRF syndrome, mitochondrial DNA mutations, tRNALys, A8344G mutation, mitochondrial translation, mitochondrial membrane potential, siRNA knockdown, human fibroblasts
MeSH terms
Anticodon, Cell Nucleus, Cells, Cultured, Electron Transport Complex IV, Cytoplasm, DNA, DNA, Mitochondrial, Fibroblasts, Humans, Mitochondria, Mutation, RNA, Transfer, Lys, Saccharomyces cerevisiae, Protein Biosynthesis, MERRF Syndrome, RNA Transport, RNA, Small Interfering

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