ArticleNature chemical biology2025
Mitochondria-localized MBD2c facilitates mtDNA transcription and drug resistance.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- SUMOylation in Mitochondrial Quality Control: Mechanisms and Implications for Neurodegenerative Disease.Molecular neurobiology · 2026Review
- Spatiotemporal analysis of reactive oxygen species using specific activity-based sensing fluorescent imaging probes.Nature reviews. Chemistry · 2026Review
- Alternative splicing rewires breast cancer and opens therapeutic avenues.Cell communication and signaling : CCS · 2026Review
- Physical Exercise Counteracts Impaired Cognition by Improving Mitochondrial Function.International journal of molecular sciences · 2026Review
- Jionoside B1 Sensitizes TNBC to Cisplatin by Inhibiting SIRT3-Mediated Oxidative Stress Defense.Biomedicines · 2026Article
- Mitochondrial LINC01133 regulates pyroptosis and calcium homeostasis in cisplatin-resistant lung adenocarcinoma.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Targeting the TFAM-cGAS-STING axis: a mitochondrial-inflammatory link in the pathogenesis and treatment of diabetic kidney disease.International urology and nephrology · 2026Review
- Mitochondrial DNA methylation is involved in contrast-induced renal tubular epithelial cell injury.Renal failure · 2025Article
- Decoding the lactylation-immune link in calcific aortic valve disease: a comprehensive bioinformatics approach.Human genomics · 2025Article
- Targeting Mitochondrial Quality Control for the Treatment of Triple-Negative Breast Cancer: From Molecular Mechanisms to Precision Therapy.Biomolecules · 2025Review
- The role of MBD2 in immune cell development, function, and autoimmune diseases.Cell death discovery · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Mitochondria contain a 16-kb double stranded DNA genome encoding 13 proteins essential for respiration, but the mechanisms regulating transcription and their potential role in cancer remain elusive. Although methyl-CpG-binding domain (MBD) proteins are essential for nuclear transcription, their role in mitochondrial DNA (mtDNA) transcription is unknown. Here we report that the MBD2c splicing variant translocates into mitochondria to mediate mtDNA transcription and increase mitochondrial respiration in triple-negative breast cancer (TNBC) cells. In particular, MBD2c binds the noncoding region in mtDNA and interacts with SIRT3, which in turn deacetylates and activates TFAM, a primary mitochondrial transcription factor, leading to enhanced mtDNA transcription. Furthermore, MBD2c recovered the decreased mitochondrial gene expression caused by the DNA synthesis inhibitor cisplatin, preserving mitochondrial respiration and consequently enhancing drug resistance and proliferation in TNBC cells. These data collectively demonstrate that MBD2c positively regulates mtDNA transcription, thus connecting epigenetic regulation by deacetylation with cancer cell metabolism, suggesting druggable targets to overcome resistance.
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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.