ArticleMechanisms of ageing and development
The role of DMQ(9) in the long-lived mutant clk-1.
Article in Mechanisms of ageing and development. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 27 citations in OpenAlex.
- Homozygous COQ7 mutation: a new cause of potentially treatable distal hereditary motor neuropathy.Brain : a journal of neurology · 2023Article
- A novelMolecular genetics and metabolism reports · 2022Article
- Role of oxidation of excitation-contraction coupling machinery in age-dependent loss of muscle function ineLife · 2022Article
- Animal Models of Coenzyme Q Deficiency: Mechanistic and Translational Learnings.Antioxidants (Basel, Switzerland) · 2021Review
- β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight.Biomedicines · 2021Article
- Minimal mitochondrial respiration is required to prevent cell death by inhibition of mTOR signaling in CoQ-deficient cells.Cell death discovery · 2021Article
- Metabolic Targets of Coenzyme Q10 in Mitochondria.Antioxidants (Basel, Switzerland) · 2021Review
- Rapamycin administration is not a valid therapeutic strategy for every case of mitochondrial disease.EBioMedicine · 2019Article
- β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype inEMBO molecular medicine · 2019Article
- Cell Biology of the Mitochondrion.Genetics · 2017Review
- Pathogenicity of two COQ7 mutations and responses to 2,4-dihydroxybenzoate bypass treatment.Journal of cellular and molecular medicine · 2017Article
- Invertebrate models for coenzyme q10 deficiency.Molecular syndromology · 2014Article
- Genetic variability of respiratory complex abundance, organization and activity in mouse brain.Genes, brain, and behavior · 2014Article
- Mitochondrial respiration without ubiquinone biosynthesis.Human molecular genetics · 2013Article
- Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel.Biochimica et biophysica acta · 2013Review
- A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae.Biochimica et biophysica acta · 2013Article
- Article
- The genetics of isoflurane-induced developmental neurotoxicity.Neurotoxicology and teratologyArticle
- Molecular genetics of ubiquinone biosynthesis in animals.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
introductionUbiquinone (UQ) is a redox active lipid that transfers electrons from complex I or II to complex III in the electron transport chain (ETC). The long-lived Caenorhabditis elegans mutant clk-1 is unable to synthesize its native ubiquinone, and accumulates high amounts of its precursor, 5-demethoxyubiquinone-9 (DMQ(9)). In clk-1, complexes I-III activity is inhibited while complexes II-III activity is normal. We asked whether the complexes I-III defect in clk-1 was caused by: (1) a defect in the ETC; (2) an inhibitory effect of DMQ(9); or (3) a decreased amount of ubiquinone.
methodsWe extracted the endogenous quinones from wildtype (N2) and clk-1 mitochondria, replenished them with exogenous ubiquinones, and measured ETC activities.
resultsReplenishment of extracted mutant and wildtype mitochondria resulted in equal enzymatic activities for complexes I-III and II-III ETC assays. Blue native gels showed that supercomplex formation was indistinguishable between clk-1 and N2. The addition of a pentane extract from clk-1 mitochondria containing DMQ(9) to wildtype mitochondria specifically inhibited complexes I-III activity. UQ in clk-1 mitochondria was oxidized compared to N2. DISCUSSION: Our results show that no measurable intrinsic ETC defect exists in clk-1 mitochondria. The data indicate that DMQ(9) specifically inhibits electron transfer from complex I to ubiquinone.
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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.