ArticleNucleic acids research2011
Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task?
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 150 citations in OpenAlex.
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Mitochondrial cardiomyopathy: bridging molecular mechanisms and clinical frontiers.Nature reviews. Cardiology · 2026Review
- Mitochondrial flagella-like extensions (MitoFLARE) dysfunction triggers STING-mediated immune dysregulation in sepsis.Nature communications · 2026Article
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Exogenous expression of ATP8, a mitochondrial encoded protein, from the nucleusMolecular therapy. Methods & clinical development · 2024Article
- A High-Throughput Colocalization Pipeline for Quantification of Mitochondrial Targeting across Different Protein Types.ACS synthetic biology · 2023Article
- Modeling mitochondrial DNA diseases: from base editing to pluripotent stem-cell-derived organoids.EMBO reports · 2023Review
- High-throughput colocalization pipeline quantifies efficacy of mitochondrial targeting signals across different protein types.bioRxiv : the preprint server for biology · 2023Article
- Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model.Frontiers in neuroscience · 2023Article
- Current advances in gene therapy of mitochondrial diseases.Journal of translational medicine · 2022Review
- Gene therapy for primary mitochondrial diseases: experimental advances and clinical challenges.Nature reviews. Neurology · 2022Review
- Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the YeastInternational journal of molecular sciences · 2022Article
- Overexpression of cytosolic long noncoding RNA cytb protects against pressure-overload-induced heart failure via sponging microRNA-103-3p.Molecular therapy. Nucleic acids · 2022Article
- The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics.Biomedicines · 2022Review
- Mitochondrial Retinopathies.International journal of molecular sciences · 2021Review
- Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson's Disease.Genes · 2021Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial-DNA diseases have no effective treatments. Allotopic expression-synthesis of a wild-type version of the mutated protein in the nuclear-cytosolic compartment and its importation into mitochondria-has been proposed as a gene-therapy approach. Allotopic expression has been successfully demonstrated in yeast, but in mammalian mitochondria results are contradictory. The evidence available is based on partial phenotype rescue, not on the incorporation of a functional protein into mitochondria. Here, we show that reliance on partial rescue alone can lead to a false conclusion of successful allotopic expression. We recoded mitochondrial mt-Nd6 to the universal genetic code, and added the N-terminal mitochondrial-targeting sequence of cytochrome c oxidase VIII (C8) and the HA epitope (C8Nd6HA). The protein apparently co-localized with mitochondria, but a significant part of it seemed to be located outside mitochondria. Complex I activity and assembly was restored, suggesting successful allotopic expression. However, careful examination of transfected cells showed that the allotopically-expressed protein was not internalized in mitochondria and that the selected clones were in fact revertants for the mt-Nd6 mutation. These findings demonstrate the need for extreme caution in the interpretation of functional rescue experiments and for clear-cut controls to demonstrate true rescue of mitochondrial function by allotopic expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.