ArticleInvestigative ophthalmology & visual science2021
Assocation Between Leber's Hereditary Optic Neuropathy and MT-ND1 3460G>A Mutation-Induced Alterations in Mitochondrial Function, Apoptosis, and Mitophagy.
Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Pooled it
- CLRN1 Variants in Müller Cells Cause Mitochondrial Dysfunction in USH3A Retinal Organoids.CNS neuroscience & therapeutics · 2026Article
- Molecular Mechanism of Mitochondrial Complex I Disruption by m.14484T>C Underlying Leber Hereditary Optic Neuropathy.bioRxiv : the preprint server for biology · 2026Article
- The role of energy deficit in autophagy failure in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- [Pathogenic mechanisms of Leber hereditary optic neuropathy caused by m.3472T>C mutation].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Article
- Development of Two In Vitro ND1-LHON Models for Evaluating Gene Therapy Efficacy.Investigative ophthalmology & visual science · 2025Article
- Vitamin A treatment restores vision failures arising from Leber's hereditary optic neuropathy-linked mtDNA mutation.JCI insight · 2025Article
- The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization.International journal of molecular sciences · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Establishment of human Leber's hereditary optic neuropathy model using iPSC-derived retinal organoids.Frontiers in cellular neuroscience · 2025Article
- Mitochondrial complex I subunitHeliyon · 2024Review
- Deficient tRNA posttranscription modification dysregulated the mitochondrial quality controls and apoptosis.iScience · 2024Article
- Red Flags in Primary Mitochondrial Diseases: What Should We Recognize?International journal of molecular sciences · 2023Review
- How defective mitochondrial electrical activity leads to inherited blindness.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Coenzyme Q10 trapping in mitochondrial complex I underlies Leber's hereditary optic neuropathy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations.Journal of biomedical science · 2023Review
- Abnormal morphology and function in retinal ganglion cells derived from patients-specific iPSCs generated from individuals with Leber's hereditary optic neuropathy.Human molecular genetics · 2023Article
- Pathological and Therapeutic Advances in Parkinson's Disease: Mitochondria in the Interplay.Journal of Alzheimer's disease : JAD · 2023Review
- Modeling Reactive Oxygen Species-Induced Axonal Loss in Leber Hereditary Optic Neuropathy.Biomolecules · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: To investigate the molecular mechanism underlying the Leber's hereditary optic neuropathy (LHON)-linked MT-ND1 3460G>A mutation. Methods: Cybrid cell models were generated by fusing mitochondrial DNA-less ρ0 cells with enucleated cells from a patient carrying the m.3460G>A mutation and a control subject. The impact of m.3460G>A mutations on oxidative phosphorylation was evaluated using Blue Native gel electrophoresis, and measurements of oxygen consumption were made with an extracellular flux analyzer. Assessment of reactive oxygen species (ROS) production in cell lines was performed by flow cytometry with MitoSOX Red reagent. Assays for apoptosis and mitophagy were undertaken via immunofluorescence analysis. Results: Nineteen Chinese Han pedigrees bearing the m.3460G>A mutation exhibited variable penetrance and expression of LHON. The m.3460G>A mutation altered the structure and function of MT-ND1, as evidenced by reduced MT-ND1 levels in mutant cybrids bearing the mutation. The instability of mutated MT-ND1 manifested as defects in the assembly and activity of complex I, respiratory deficiency, diminished mitochondrial adenosine triphosphate production, and decreased membrane potential, in addition to increased production of mitochondrial ROS in the mutant cybrids carrying the m.3460G>A mutation. The m.3460G>A mutation mediated apoptosis, as evidenced by the elevated release of cytochrome c into the cytosol and increasing levels of the apoptotic-associated proteins BAK, BAX, and PARP, as well as cleaved caspases 3, 7, and 9, in the mutant cybrids. The cybrids bearing the m.3460G>A mutation exhibited reduced levels of autophagy protein light chain 3, accumulation of autophagic substrate P62, and impaired PTEN-induced kinase 1/parkin-dependent mitophagy. Conclusions: Our findings highlight the critical role of m.3460G>A mutation in the pathogenesis of LHON, manifested by mitochondrial dysfunction and alterations in apoptosis and mitophagy.
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