ArticleBMC molecular and cell biology2021
Complex II subunit SDHD is critical for cell growth and metabolism, which can be partially restored with a synthetic ubiquinone analog.
Article in BMC molecular and cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Human brown fat metabolism associates with systemic branched-chain amino acids homeostasis.Molecular metabolism · 2026Article
- MBD1-Mediated SDHD Methylation Aggravates Preeclampsia Progression via Triggering Mitochondrial Dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Sex-dependent differences in bioenergetics of young mouse brain microvasculature: implications for oxygen-glucose deprivation and reoxygenation injury.American journal of physiology. Heart and circulatory physiology · 2026Article
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- Exercise promotes cognition and hippocampal mitochondrial complex II expression in female rats.Experimental physiology · 2025Article
- Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasis.Nature communications · 2025Article
- Increased Exercise Tolerance in G6PD African Variant Mice Driven by Metabolic Adaptations and Erythrophagocytosis.Antioxidants (Basel, Switzerland) · 2025Article
- Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.Cancer & metabolism · 2024Article
- Article
- 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
- Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE).Cancer & metabolism · 2024Article
- Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction ofBiochemistry and biophysics reports · 2024Article
- Two sisters diagnosed with familial paraganglioma syndrome type 1 (FPGL1) and multiple endocrine neoplasia type 2A (MEN2A).World journal of surgical oncology · 2024Article
- Cellular succinate metabolism and signaling in inflammation: implications for therapeutic intervention.Frontiers in immunology · 2024Review
- Complex II ambiguities-FADHThe Journal of biological chemistry · 2024Review
- Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology.Antioxidants & redox signaling · 2023Review
- Biological Consequences of Vanadium Effects on Formation of Reactive Oxygen Species and Lipid Peroxidation.International journal of molecular sciences · 2023Review
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3 authors.
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Abstract
backgroundSuccinate dehydrogenase (Complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the mitochondrial Krebs cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC). Mutations in Complex II are associated with a number of pathologies. SDHD, one of the four subunits of Complex II, serves by anchoring the complex to the inner-membrane and transferring electrons from the complex to ubiquinone. Thus, modeling SDHD dysfunction could be a valuable tool for understanding its importance in metabolism and developing novel therapeutics, however no suitable models exist.
resultsVia CRISPR/Cas9, we mutated SDHD in HEK293 cells and investigated the in vitro role of SDHD in metabolism. Compared to the parent HEK293, the knockout mutant HEK293ΔSDHD produced significantly less number of cells in culture. The mutant cells predictably had suppressed Complex II-mediated mitochondrial respiration, but also Complex I-mediated respiration. SDHD mutation also adversely affected glycolytic capacity and ATP synthesis. Mutant cells were more apoptotic and susceptible to necrosis. Treatment with the mitochondrial therapeutic idebenone partially improved oxygen consumption and growth of mutant cells.
conclusionsOverall, our results suggest that SDHD is vital for growth and metabolism of mammalian cells, and that respiratory and growth defects can be partially restored with treatment of a ubiquinone analog. This is the first report to use CRISPR/Cas9 approach to construct a knockout SDHD cell line and evaluate the efficacy of an established mitochondrial therapeutic candidate to improve bioenergetic capacity.
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