ArticleNucleic acids research2013
Negative regulation of mitochondrial transcription by mitochondrial topoisomerase I.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- DRP lyase deficient DNA polymerase beta impairs mitochondrial electron transport chain and compromise mitochondrial DNA integrity.Research square · 2026Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT.Human molecular genetics · 2023Article
- Key hepatoprotective roles of mitochondria in liver regeneration.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- Two type I topoisomerases maintain DNA topology in human mitochondria.Nucleic acids research · 2022Article
- Functional characterization of two variants of mitochondrial topoisomerase TOP1MT that impact regulation of the mitochondrial genome.The Journal of biological chemistry · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
- Controlling the topology of mammalian mitochondrial DNA.Open biology · 2021Review
- Beyond the unwinding: role of TOP1MT in mitochondrial translation.Cell cycle (Georgetown, Tex.) · 2019Review
- Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance.International journal of molecular sciences · 2019Review
- Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A.Frontiers in genetics · 2019Review
- Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2.Nucleic acids research · 2018Article
- Mitochondrial tyrosyl-DNA phosphodiesterase 2 and its TDP2EMBO reports · 2018Article
- Topoisomerases as anticancer targets.The Biochemical journal · 2018Review
- Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription.The Journal of biological chemistry · 2017Article
- Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.Science advances · 2017Article
- Physiological Roles of DNA Double-Strand Breaks.Journal of nucleic acids · 2017Review
- Topological requirements of the mitochondrial heavy-strand promoters.Transcription · 2017Article
- Human Mitochondrial DNA-Protein Complexes Attach to a Cholesterol-Rich Membrane Structure.Scientific reports · 2015Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Mitochondrial topoisomerase I is a genetically distinct mitochondria-dedicated enzyme with a crucial but so far unknown role in the homeostasis of mitochondrial DNA metabolism. Here, we present data suggesting a negative regulatory function in mitochondrial transcription or transcript stability. Deficiency or depletion of mitochondrial topoisomerase I increased mitochondrial transcripts, whereas overexpression lowered mitochondrial transcripts, depleted respiratory complexes I, III and IV, decreased cell respiration and raised superoxide levels. Acute depletion of mitochondrial topoisomerase I triggered neither a nuclear mito-biogenic stress response nor compensatory topoisomerase IIβ upregulation, suggesting the concomitant increase in mitochondrial transcripts was due to release of a local inhibitory effect. Mitochondrial topoisomerase I was co-immunoprecipitated with mitochondrial RNA polymerase. It selectively accumulated and rapidly exchanged at a subset of nucleoids distinguished by the presence of newly synthesized RNA and/or mitochondrial RNA polymerase. The inactive Y559F-mutant behaved similarly without affecting mitochondrial transcripts. In conclusion, mitochondrial topoisomerase I dampens mitochondrial transcription and thereby alters respiratory capacity. The mechanism involves selective association of the active enzyme with transcriptionally active nucleoids and a direct interaction with mitochondrial RNA polymerase. The inhibitory role of topoisomerase I in mitochondrial transcription is strikingly different from the stimulatory role of topoisomerase I in nuclear transcription.
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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.