ArticleHuman molecular genetics2013
The cytochrome b p.278Y>C mutation causative of a multisystem disorder enhances superoxide production and alters supramolecular interactions of respiratory chain complexes.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed.
- Adult Leigh Syndrome Associated with the m.15635T>C Mitochondrial DNA Variant Affecting the CytochromeInternational journal of molecular sciences · 2025Article
- Article
- NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors.Open biology · 2022Article
- Molecular and biochemical regulation of skeletal muscle metabolism.Journal of animal science · 2022Article
- Inducing respiratory complex I impairment elicits an increase in PGC1α in ovarian cancer.Scientific reports · 2022Article
- Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain.International journal of molecular sciences · 2021Review
- NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate.Cell reports · 2021Article
- Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences.Life (Basel, Switzerland) · 2021Review
- Catalytic Reactions and Energy Conservation in the CytochromeChemical reviews · 2021Review
- Fine-tuning of the respiratory complexes stability and supercomplexes assembly in cells defective of complex III.Biochimica et biophysica acta. Bioenergetics · 2020Article
- Mitochondrial genome analysis in penile carcinoma.Molecular biology reports · 2018Article
- The Organization of Mitochondrial Supercomplexes is Modulated by Oxidative Stress In Vivo in Mouse Models of Mitochondrial Encephalopathy.International journal of molecular sciences · 2018Article
- Unravelling the Effects of the Mutation m.3571insC/MT-ND1 on Respiratory Complexes Structural Organization.International journal of molecular sciences · 2018Article
- Complex II phosphorylation is triggered by unbalanced redox homeostasis in cells lacking complex III.Biochimica et biophysica acta. Bioenergetics · 2018Article
- Quercetin-Induced Lifespan Extension inFrontiers in genetics · 2018Article
- Article
- Mitochondrial disease-related mutations at the cytochrome b-iron-sulfur protein (ISP) interface: Molecular effects on the large-scale motion of ISP and superoxide generation studied in Rhodobacter capsulatus cytochrome bc1.Biochimica et biophysica acta · 2016Article
- Cystic fibrosis-related oxidative stress and intestinal lipid disorders.Antioxidants & redox signaling · 2015Review
- Respiratory supercomplexes: plasticity and implications.Frontiers in bioscience (Landmark edition) · 2015Review
- Traffic within the cytochrome b6f lipoprotein complex: gating of the quinone portal.Biophysical journal · 2014Article
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Abstract
Cytochrome b is the only mtDNA-encoded subunit of the mitochondrial complex III (CIII), the functional bottleneck of the respiratory chain. Previously, the human cytochrome b missense mutation m.15579A>G, which substitutes the Tyr 278 with Cys (p.278Y>C), was identified in a patient with severe exercise intolerance and multisystem manifestations. In this study, we characterized the biochemical properties of cybrids carrying this mutation and report that the homoplasmic p.278Y>C mutation caused a dramatic reduction in the CIII activity and in CIII-driven mitochondrial ATP synthesis. However, the CI, CI + CIII and CII + CIII activities and the rate of ATP synthesis driven by the CI or CII substrate were only partially reduced or unaffected. Consistent with these findings, mutated cybrids maintained the mitochondrial membrane potential in the presence of oligomycin, indicating that it originated from the respiratory electron transport chain. The p.278Y>C mutation enhanced superoxide production, as indicated by direct measurements in mitochondria and by the imbalance of glutathione homeostasis in intact cybrids. Remarkably, although the assembly of CI or CIII was not affected, the examination of respiratory supercomplexes revealed that the amounts of CIII dimer and III2IV1 were reduced, whereas those of I1III2IVn slightly increased. We therefore suggest that the deleterious effects of p.278Y>C mutation on cytochrome b are palliated when CIII is assembled into the supercomplexes I1III2IVn, in contrast to when it is found alone. These findings underline the importance of supramolecular interactions between complexes for maintaining a basal respiratory chain activity and shed light to the molecular basis of disease manifestations associated with this mutation.
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