ArticleThe Journal of biological chemistry2022
Functional characterization of two variants of mitochondrial topoisomerase TOP1MT that impact regulation of the mitochondrial genome.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Age-associated G-quadruplex accumulation and DDX5 loss shape chromatin landscapes in human astrocytes.Research square · 2025Article
- The MFN2 Q367H variant reveals a novel pathomechanism connected to mtDNA-mediated inflammation.Life science alliance · 2025Article
- Mitochondrial DNA depletion syndrome and its cardiac complication.Frontiers in cardiovascular medicine · 2025Review
- Gene Expression Dysregulation in Whole Blood of Patients withInternational journal of molecular sciences · 2024Article
- Mitochondrial topoisomerase I (Top1MT) prevents the onset of metabolic dysfunction-associated steatohepatitis (MASH) in mice.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial DNA release and sensing in innate immune responses.Human molecular genetics · 2024Review
- Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer.Cancer & metabolism · 2024Article
- Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT.Human molecular genetics · 2023Article
- Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
TOP1MT encodes a mitochondrial topoisomerase that is important for mtDNA regulation and is involved in mitochondrial replication, transcription, and translation. Two variants predicted to affect TOP1MT function (V1 - R198C and V2 - V338L) were identified by exome sequencing of a newborn with hypertrophic cardiomyopathy. As no pathogenic TOP1MT variants had been confirmed previously, we characterized these variants for their ability to rescue several TOP1MT functions in KO cells. Consistent with these TOP1MT variants contributing to the patient phenotype, our comprehensive characterization suggests that both variants had impaired activity. Critically, we determined neither variant was able to restore steady state levels of mitochondrial-encoded proteins nor to rescue oxidative phosphorylation when re-expressed in TOP1MT KO cells. However, we found the two variants behaved differently in some respects; while the V1 variant was more efficient in restoring transcript levels, the V2 variant showed better rescue of mtDNA copy number and replication. These findings suggest that the different TOP1MT variants affect distinct TOP1MT functions. Altogether, these findings begin to provide insight into the many roles that TOP1MT plays in the maintenance and expression of the mitochondrial genome and how impairments in this important protein may lead to human pathology.
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