ArticleBrain : a journal of neurology2014
Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.
Article in Brain : a journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 2 of them syntheses that pooled it.
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Who cites it
159 citing papers in PubMed, 2 syntheses or guidelines pooled it, 283 citations in OpenAlex.
- Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.European journal of neurology · 2025Pooled it
- Psychological Stress and Mitochondria: A Systematic Review.Psychosomatic medicinePooled it
- Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy.Investigative ophthalmology & visual science · 2025Trial
- A NovelInternational journal of molecular sciences · 2026Article
- Associations Between Neuromuscular Fatigue, Anxiety, and Peripheral Biomarkers of Neuronal Injury, Inflammation, and Mitochondrial Dysfunction in Treatment-Naïve Relapsing-Remitting Multiple Sclerosis.Brain and behavior · 2026Article
- Individualised mapping of living human brain mitochondria by MRI reveals signatures of bioenergetic defects.Research square · 2026Article
- Individual and joint association of maternal and cord blood mitochondrial DNA heteroplasmy and copy number with preterm birth.Pediatric research · 2026Article
- Analysis of genetic risk factors for Leber hereditary optic neuropathy in the Polish population.Journal of applied genetics · 2026Article
- Investigating PeripheralBiomolecules · 2026Article
- Mitochondrial cardiomyopathy: bridging molecular mechanisms and clinical frontiers.Nature reviews. Cardiology · 2026Review
- Individualised mapping of living human brain mitochondria by MRI reveals signatures of bioenergetic defects.bioRxiv : the preprint server for biology · 2026Article
- Targeting the Mitochondrial Phenotype in Cockayne Syndrome Patient Cells: From Bioenergetic Fragility to Pharmacologic Rescue.bioRxiv : the preprint server for biology · 2026Article
- Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics.Nature communications · 2026Article
- Modifier variants in metabolic pathways are associated with an increased penetrance of Leber's Hereditary Optic Neuropathy.European journal of human genetics : EJHG · 2026Article
- Combination treatment with antioxidants and creatine alleviates common and variant-specific mitochondrial impairments in Leber's hereditary optic neuropathy patient-derived fibroblasts.Human molecular genetics · 2025Article
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Nitric Oxide May Adversely Affect the Metabolism and Viability of Retinal Organoids Derived from Patients with Leber Hereditary Optic Neuropathy.The American journal of pathology · 2025Article
- DJ-1 deficiency and aging: dual drivers of retinal mitochondrial dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- Selection Increases Mitonuclear DNA Discordance but Reconciles Incompatibility in African Cattle.Molecular biology and evolution · 2025Article
99 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 10 institutions in 4 countries.
Funding
Abstract
Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.
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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.