ArticleNature communications2025
Ubiquinol-mediated suppression of mitochondria-associated ferroptosis is a targetable function of lactate dehydrogenase B in cancer.
Article in Nature communications, 2025. 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.
- Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Integrated OAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- Flavonoid compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming.Journal of pharmaceutical analysis · 2026Article
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- [SENP1 reduces ferroptosis of thyroid cancer cells by regulating hypoxia-inducible factor-1α].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- Lactate Dehydrogenase B delactylation promotes gastric cancer metastasis via enhancing glutathione-mediated resistance to ferroptosis.Cell biology and toxicology · 2026Article
- STING synergizes with TOX suppressing HO-1 expression to trigger ferroptosis in tumor-infiltrating CD8+ T cell and immunotherapy resistance.Nature communications · 2026Article
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Beyond metabolism: exploring the regulatory and therapeutic implications of lactate and lactylation in cancer-regulated cell death.Cell death & disease · 2026Review
- Ubiquinol in Fertility and Reproduction: A Conditionally Essential Nutrient for Critical Early-Life Stages.Nutrients · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Ferroptosis as an Emerging Therapeutic Target in Allergic Diseases.Drug design, development and therapy · 2026Review
- Do fungi also undergo "ferroptosis"? A microscopic exploration of cellular death.Apoptosis : an international journal on programmed cell death · 2025Review
- Lactylation in cancer biology: Unlocking new avenues for research and therapy.Cancer communications (London, England) · 2025Review
- The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis.Nature communications · 2025Article
- Inhibition of LDHB triggers DNA damage and increases cisplatin sensitivity in pleural mesothelioma.Oncogenesis · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Lactate dehydrogenase B (LDHB) fuels oxidative cancer cell metabolism by converting lactate to pyruvate. This study uncovers LDHB's role in countering mitochondria-associated ferroptosis independently of lactate's function as a carbon source. LDHB silencing alters mitochondrial morphology, causes lipid peroxidation, and reduces cancer cell viability, which is potentiated by the ferroptosis inducer RSL3. Unlike LDHA, LDHB acts in parallel with glutathione peroxidase 4 (GPX4) and dihydroorotate dehydrogenase (DHODH) to suppress mitochondria-associated ferroptosis by decreasing the ubiquinone (coenzyme Q, CoQ) to ubiquinol (CoQH2) ratio. Indeed, supplementation with mitoCoQH2 (mitochondria-targeted analogue of CoQH2) suppresses mitochondrial lipid peroxidation and cell death after combined LDHB silencing and RSL3 treatment, consistent with the presence of LDHB in the cell fraction containing the mitochondrial inner membrane. Addressing the underlying molecular mechanism, an in vitro NADH consumption assay with purified human LDHB reveals that LDHB catalyzes the transfer of reducing equivalents from NADH to CoQ and that the efficiency of this reaction increases by the addition of lactate. Finally, radiation therapy induces mitochondrial lipid peroxidation and reduces tumor growth, which is further enhanced when combined with LDHB silencing. Thus, LDHB-mediated lactate oxidation drives the CoQ-dependent suppression of mitochondria-associated ferroptosis, a promising target for combination therapies.
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