ArticlePLoS genetics2011
Evolution meets disease: penetrance and functional epistasis of mitochondrial tRNA mutations.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Mitochondrial DNA mutations in head and neck squamous cell carcinoma: a systematic review and meta-analysis.BMC cancer · 2025Pooled it
- Correction of pathogenic mitochondrial DNA in patient-derived disease models using mitochondrial base editors.PLoS biology · 2025Article
- The GPI-anchor biosynthesis pathway is critical for syncytiotrophoblast differentiation and placental development.Cellular and molecular life sciences : CMLS · 2024Article
- A Mutation in Mouse MT-ATP6 Gene Induces Respiration Defects and Opposed Effects on the Cell Tumorigenic Phenotype.International journal of molecular sciences · 2023Article
- Cellular mechanisms of mtDNA heteroplasmy dynamics.Critical reviews in biochemistry and molecular biology · 2021Review
- The regulatory roles of aminoacyl-tRNA synthetase in cardiovascular disease.Molecular therapy. Nucleic acids · 2021Review
- Not all mitochondrial DNAs are made equal and the nucleus knows it.IUBMB life · 2021Review
- Intimate Relations-Mitochondria and Ageing.International journal of molecular sciences · 2020Review
- Age Dependent Dysfunction of Mitochondrial and ROS Metabolism Induced by Mitonuclear Mismatch.Frontiers in genetics · 2019Article
- Mitochondrial Complex I activity signals antioxidant response through ERK5.Scientific reports · 2018Article
- Defects in the mitochondrial-tRNA modification enzymes MTO1 and GTPBP3 promote different metabolic reprogramming through a HIF-PPARγ-UCP2-AMPK axis.Scientific reports · 2018Article
- Structural impairment patterns in peripapillary retinal fiber layer and retinal ganglion cell layer in mitochondrial optic neuropathies.International journal of ophthalmology · 2018Article
- microRNA-mediated differential expression of TRMU, GTPBP3 and MTO1 in cell models of mitochondrial-DNA diseases.Scientific reports · 2017Article
- Sex-specific influences of mtDNA mitotype and diet on mitochondrial functions and physiological traits in Drosophila melanogaster.PloS one · 2017Article
- Mitochondrial Quality Control as a Therapeutic Target.Pharmacological reviews · 2016Review
- A Drosophila model for mito-nuclear diseases generated by an incompatible interaction between tRNA and tRNA synthetase.Disease models & mechanisms · 2015Article
- Article
- Mitonuclear interactions: evolutionary consequences over multiple biological scales.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- Screen for mitochondrial DNA copy number maintenance genes reveals essential role for ATP synthase.Molecular systems biology · 2014Article
- The emergence of the mitochondrial genome as a partial regulator of nuclear function is providing new insights into the genetic mechanisms underlying age-related complex disease.Human genetics · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
About half of the mitochondrial DNA (mtDNA) mutations causing diseases in humans occur in tRNA genes. Particularly intriguing are those pathogenic tRNA mutations than can reach homoplasmy and yet show very different penetrance among patients. These mutations are scarce and, in addition to their obvious interest for understanding human pathology, they can be excellent experimental examples to model evolution and fixation of mitochondrial tRNA mutations. To date, the only source of this type of mutations is human patients. We report here the generation and characterization of the first mitochondrial tRNA pathological mutation in mouse cells, an m.3739G>A transition in the mitochondrial mt-Ti gene. This mutation recapitulates the molecular hallmarks of a disease-causing mutation described in humans, an m.4290T>C transition affecting also the human mt-Ti gene. We could determine that the pathogenic molecular mechanism, induced by both the mouse and the human mutations, is a high frequency of abnormal folding of the tRNA(Ile) that cannot be charged with isoleucine. We demonstrate that the cells harboring the mouse or human mutant tRNA have exacerbated mitochondrial biogenesis triggered by an increase in mitochondrial ROS production as a compensatory response. We propose that both the nature of the pathogenic mechanism combined with the existence of a compensatory mechanism can explain the penetrance pattern of this mutation. This particular behavior can allow a scenario for the evolution of mitochondrial tRNAs in which the fixation of two alleles that are individually deleterious can proceed in two steps and not require the simultaneous mutation of both.
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Registered trials
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