ArticleMolecular pharmacology2014
Poisoning of mitochondrial topoisomerase I by lamellarin D.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 64 citations in OpenAlex.
- Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer.Cancer & metabolism · 2024Article
- Pyrrolo[2,1-RSC advances · 2024Review
- Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure-activity relationships.RSC advances · 2023Article
- Article
- A comprehensive pan-cancer analysis of the expression characteristics, prognostic value, and immune characteristics ofFrontiers in genetics · 2022Article
- SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy.Science advances · 2019Article
- Beyond the unwinding: role of TOP1MT in mitochondrial translation.Cell cycle (Georgetown, Tex.) · 2019Review
- Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair.International journal of molecular sciences · 2019Review
- Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance.International journal of molecular sciences · 2019Review
- Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids.Chemical science · 2019Article
- Ascidian Toxins with Potential for Drug Development.Marine drugs · 2018Review
- Marine Mollusk-Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance.Medicinal research reviews · 2017Review
- Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.Science advances · 2017Article
- Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases.Current genomics · 2017Review
- Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.Nature reviews. Molecular cell biology · 2016Review
- topIb, a phylogenetic hallmark gene of Thaumarchaeota encodes a functional eukaryote-like topoisomerase IB.Nucleic acids research · 2016Article
- Article
- Single-Molecule Supercoil Relaxation Assay as a Screening Tool to Determine the Mechanism and Efficacy of Human Topoisomerase IB Inhibitors.Molecular cancer therapeutics · 2015Article
- Anticancer properties of lamellarins.Marine drugs · 2015Review
- Synthetic approaches to the lamellarins--a comprehensive review.Marine drugs · 2014Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Lamellarin D (Lam-D) is a hexacyclic pyrole alkaloid isolated from marine invertebrates, whose biologic properties have been attributed to mitochondrial targeting. Mitochondria contain their own DNA (mtDNA), and the only specific mitochondrial topoisomerase in vertebrates is mitochondrial topoisomerase I (Top1mt). Here, we show that Top1mt is a direct mitochondrial target of Lam-D. In vitro Lam-D traps Top1mt and induces Top1mt cleavage complexes (Top1mtcc). Using single-molecule analyses, we also show that Lam-D slows down supercoil relaxation of Top1mt and strongly inhibits Top1mt religation in contrast to the inefficacy of camptothecin on Top1mt. In living cells, we show that Lam-D accumulates rapidly inside mitochondria, induces cellular Top1mtcc, and leads to mtDNA damage. This study provides evidence that Top1mt is a direct mitochondrial target of Lam-D and suggests that developing Top1mt inhibitors represents a novel strategy for targeting mitochondrial DNA.
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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.