ArticleProceedings of the National Academy of Sciences of the United States of America2015
Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver regeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Iron Homeostasis and Liver Diseases.Journal of cellular and molecular medicine · 2026Review
- DRP lyase deficient DNA polymerase beta impairs mitochondrial electron transport chain and compromise mitochondrial DNA integrity.Research square · 2026Article
- Genetic and pharmaceutical manipulation of H3K9 methyltransferase Suv39h1 promotes liver regeneration by unleashing HMGB2 transcription.Experimental & molecular medicine · 2026Article
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Evaluating the mitochondrial structure and gene expression profile of regenerated liver tissues in mice after 85% partial hepatectomy.Journal of gastrointestinal oncology · 2024Article
- Mitochondrial topoisomerase I (Top1MT) prevents the onset of metabolic dysfunction-associated steatohepatitis (MASH) in mice.bioRxiv : the preprint server for biology · 2024Article
- ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nature communications · 2023Article
- Glutamine protects mouse spermatogonial stem cells against NOX1-derived ROS for sustaining self-renewal division in vitro.Development (Cambridge, England) · 2023Article
- Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT.Human molecular genetics · 2023Article
- Evolution of TOP1 and TOP1MT Topoisomerases in Chordata.Journal of molecular evolution · 2023Article
- Mitochondria-derived HCell death & disease · 2023Article
- Key hepatoprotective roles of mitochondria in liver regeneration.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- Topoisomerases in Immune Cell Development and Function.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Riboflavin ameliorates mitochondrial dysfunction via the AMPK/PGC1α/HO‑1 signaling pathway and attenuates carbon tetrachloride‑induced liver fibrosis in rats.Experimental and therapeutic medicine · 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
- Multifunctional polyphenol-based silk hydrogel alleviates oxidative stress and enhances endogenous regeneration of osteochondral defects.Materials today. Bio · 2022Article
- Aging reduces liver resiliency by dysregulating Hedgehog signaling.Aging cell · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The liver has an exceptional replicative capacity following partial hepatectomy or chemical injuries. Cellular proliferation requires increased production of energy and essential metabolites, which critically depend on the mitochondria. To determine whether Top1mt, the vertebrate mitochondrial topoisomerase, is involved in this process, we studied liver regeneration after carbon tetrachloride (CCl4) administration. TOP1mt knockout (KO) mice showed a marked reduction in regeneration and hepatocyte proliferation. The hepatic mitochondrial DNA (mtDNA) failed to increase during recovery from CCl4 exposure. Reduced glutathione was also depleted, indicating increased reactive oxygen species (ROS). Steady-state levels of ATP, O2 consumption, mtDNA, and mitochondrial mass were also reduced in primary hepatocytes from CCl4-treated KO mice. To further test whether Top1mt acted by enabling mtDNA regeneration, we tested TOP1mt KO fibroblasts and human colon carcinoma HCT116 cells and measured mtDNA after 3-d treatment with ethidium bromide. Both types of TOP1mt knockout cells showed defective mtDNA regeneration following mtDNA depletion. Our study demonstrates that Top1mt is required for normal mtDNA homeostasis and for linking mtDNA expansion with hepatocyte proliferation.
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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.