ArticleProceedings of the National Academy of Sciences of the United States of America2023
Coenzyme Q10 trapping in mitochondrial complex I underlies Leber's hereditary optic neuropathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 19 citations in OpenAlex.
- Functional and structural analysis in relation to age at onset of Leber hereditary optic neuropathy: a Swedish cohort.Eye (London, England) · 2026Article
- A timeline of structural and functional consequences to ipRGCs in a mouse model of Alzheimer's disease.Neurobiology of aging · 2026Article
- RTN4IP1 mutation and endocrine failure: clinical features and possible benefits of coenzyme Q10.Endocrine connections · 2026Article
- Molecular Mechanism of Mitochondrial Complex I Disruption by m.14484T>C Underlying Leber Hereditary Optic Neuropathy.bioRxiv : the preprint server for biology · 2026Article
- Oxidative Stress and Inflammatory Biomarkers in Aqueous Humor and Blood of Patients with Leber's Hereditary Optic Neuropathy.Antioxidants (Basel, Switzerland) · 2025Article
- Flexibility and Hydration of the QJournal of chemical information and modeling · 2025Article
- Mitochondrial medicine: "from bench to bedside" 3PM-guided concept.The EPMA journal · 2025Article
- Autosomal Recessive Leber Hereditary Optic Neuropathy Triggered by Superior Mesenteric Artery Syndrome.Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Metformin may alter the course of Leber's hereditary optic neuropathy: a case report.Frontiers in medicine · 2025Article
- The Optic Nerve at Stake: Update on Environmental Factors Modulating Expression of Leber's Hereditary Optic Neuropathy.Biomedicines · 2024Review
- Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy.Cell reports. Medicine · 2024Article
- How defective mitochondrial electrical activity leads to inherited blindness.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants.Frontiers in molecular neuroscience · 2023Article
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6 authors at 2 institutions in 1 country.
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Abstract
How does a single amino acid mutation occurring in the blinding disease, Leber's hereditary optic neuropathy (LHON), impair electron shuttling in mitochondria? We investigated changes induced by the m.3460 G>A mutation in mitochondrial protein ND1 using the tools of Molecular Dynamics and Free Energy Perturbation simulations, with the goal of determining the mechanism by which this mutation affects mitochondrial function. A recent analysis suggested that the mutation's replacement of alanine A52 with a threonine perturbs the stability of a region where binding of the electron shuttling protein, Coenzyme Q10, occurs. We found two functionally opposing changes involving the role of Coenzyme Q10. The first showed that quantum electron transfer from the terminal Fe/S complex, N2, to the Coenzyme Q10 headgroup, docked in its binding pocket, is enhanced. However, this positive adjustment is overshadowed by our finding that the mobility of Coenzyme Q10 in its oxidized and reduced states, entering and exiting its binding pocket, is disrupted by the mutation in a manner that leads to conditions promoting the generation of reactive oxygen species. An increase in reactive oxygen species caused by the LHON mutation has been proposed to be responsible for this optic neuropathy.
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