ArticleMolecular and cellular biology2008
Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers.
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Who cites it
242 citing papers in PubMed, 428 citations in OpenAlex.
- Emerging role of mitoNEET as mitochondrial sensor of hypoxia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- Succinate dehydrogenase-deficient cancer cells have increased susceptibility to Ym155-induced DNA damage.Endocrine-related cancer · 2026Article
- Oxidative stress and metabolic dysfunction in oral lichen planus pathogenesis.Animal cells and systems · 2026Review
- Case Report: The silent giant: biochemical-clinical dissociation in a large cystic pheochromocytoma.Frontiers in oncology · 2026Article
- Imaging lymphatic function and inflammation response through hypoxia via endogenous biomarker.Journal of biomedical optics · 2026Article
- NEK7 couples SDHB to orchestrate respiratory chain electron transport homeostasis that impedes liver fibrosis.Nature communications · 2025Article
- Complex II assembly drives metabolic adaptation to OXPHOS dysfunction.Science advances · 2025Article
- Inhibition of Mitochondrial Succinate Dehydrogenase with Dimethyl Malonate Promotes M2 Macrophage Polarization by Enhancing STAT6 Activation.Inflammation · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- SDH defective cancers: molecular mechanisms and treatment strategies.Cell biology and toxicology · 2025Review
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Succinate in innate immunity: linking metabolic reprogramming to immune modulation.Frontiers in immunology · 2025Review
- 6-Methoxydihydroavicine is a benzophenanthridine alkaloid with anti-leukemia activity.Frontiers in pharmacology · 2025Article
- Impacts of mitochondrial dysfunction on axonal microtubule bundles as a potential mechanism of neurodegeneration.Frontiers in neuroscience · 2025Review
- A Novel Human SDHA-Knockout Cell Line Model for the Functional Analysis of Clinically Relevant SDHA Variants.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Succinate Dehydrogenase and Human Disease: Novel Insights into a Well-Known Enzyme.Biomedicines · 2024Review
- Succinate dehydrogenase-complex II regulates skeletal muscle cellular respiration and contractility but not muscle mass in genetically induced pulmonary emphysema.Science advances · 2024Article
- Mitochondrial Dysfunction in Sporadic Amyotrophic Lateral Sclerosis Patients: Insights from High-Resolution Respirometry.Biomedicines · 2024Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice.Science translational medicine · 2024Article
182 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial complex II is a tumor suppressor comprised of four subunits (SdhA, SdhB, SdhC, and SdhD). Mutations in any of these should disrupt complex II enzymatic activity, yet defects in SdhA produce bioenergetic deficiency while defects in SdhB, SdhC, or SdhD induce tumor formation. The mechanisms underlying these differences are not known. We show that the inhibition of distal subunits of complex II, either pharmacologically or via RNA interference of SdhB, increases normoxic reactive oxygen species (ROS) production, increases hypoxia-inducible factor alpha (HIF-alpha) stabilization in an ROS-dependent manner, and increases growth rates in vitro and in vivo without affecting hypoxia-mediated activation of HIF-alpha. Proximal pharmacologic inhibition or RNA interference of complex II at SdhA, however, does not increase normoxic ROS production or HIF-alpha stabilization and results in decreased growth rates in vitro and in vivo. Furthermore, the enhanced growth rates resulting from SdhB suppression are inhibited by the suppression of HIF-1alpha and/or HIF-2alpha, indicating that the mechanism of SdhB-induced tumor formation relies upon ROS production and subsequent HIF-alpha activation. Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA.
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