ArticleDevelopment (Cambridge, England)2010
A model of Costeff Syndrome reveals metabolic and protective functions of mitochondrial OPA3.
Article in Development (Cambridge, England), 2010. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.Nature communications · 2026Article
- Neuronal Loss of the Glutamate Transporter GLT-1 Promotes Excitotoxic Injury in the Hippocampus.Frontiers in cellular neuroscience · 2021Article
- The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance.Frontiers in neuroscience · 2021Review
- Kendomycin Cytotoxicity against Bacterial, Fungal, and Mammalian Cells Is Due to Cation Chelation.Journal of natural products · 2020Article
- Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System.International journal of molecular sciences · 2019Review
- Phytanoyl-CoA 2-Hydroxylase-Interacting Protein-Like Gene Is a Therapeutic Target Gene for Glioblastoma Multiforme.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Autosomal dominant optic atrophy and cataract "plus" phenotype including axonal neuropathy.Neurology. Genetics · 2019Article
- Optic atrophy, cataracts, lipodystrophy/lipoatrophy, and peripheral neuropathy caused by a de novoCold Spring Harbor molecular case studies · 2017Article
- On the origin of 3-methylglutaconic acid in disorders of mitochondrial energy metabolism.Journal of inherited metabolic disease · 2016Article
- Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases.Scientific reports · 2016Article
- Disrupted mitochondrial function in the Opa3L122P mouse model for Costeff Syndrome impairs skeletal integrity.Human molecular genetics · 2016Article
- Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish.Frontiers in molecular neuroscience · 2016Review
- Costeff syndrome: clinical features and natural history.Journal of neurology · 2014Article
- Metabolic biology of 3-methylglutaconic acid-uria: a new perspective.Journal of inherited metabolic disease · 2014Review
- Leucine Loading Test is Only Discriminative for 3-Methylglutaconic Aciduria Due to AUH Defect.JIMD reports · 2014Article
- 3-Methylglutaconic aciduria--lessons from 50 genes and 977 patients.Journal of inherited metabolic disease · 2013Article
- Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature.Journal of inherited metabolic disease · 2013Review
- How mitochondrial dysfunction affects zebrafish development and cardiovascular function: an in vivo model for testing mitochondria-targeted drugs.British journal of pharmacology · 2013Article
- Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease.Disease models & mechanisms · 2012Article
- The 3-methylglutaconic acidurias: what's new?Journal of inherited metabolic disease · 2012Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Costeff Syndrome, which is caused by mutations in the OPTIC ATROPHY 3 (OPA3) gene, is an early-onset syndrome characterized by urinary excretion of 3-methylglutaconic acid (MGC), optic atrophy and movement disorders, including ataxia and extrapyramidal dysfunction. The OPA3 protein is enriched in the inner mitochondrial membrane and has mitochondrial targeting signals, but a requirement for mitochondrial localization has not been demonstrated. We find zebrafish opa3 mRNA to be expressed in the optic nerve and retinal layers, the counterparts of which in humans have high mitochondrial activity. Transcripts of zebrafish opa3 are also expressed in the embryonic brain, inner ear, heart, liver, intestine and swim bladder. We isolated a zebrafish opa3 null allele for which homozygous mutants display increased MGC levels, optic nerve deficits, ataxia and an extrapyramidal movement disorder. This correspondence of metabolic, ophthalmologic and movement abnormalities between humans and zebrafish demonstrates a phylogenetic conservation of OPA3 function. We also find that delivery of exogenous Opa3 can reduce increased MGC levels in opa3 mutants, and this reduction requires the mitochondrial localization signals of Opa3. By manipulating MGC precursor availability, we infer that elevated MGC in opa3 mutants derives from extra-mitochondrial HMG-CoA through a non-canonical pathway. The opa3 mutants have normal mitochondrial oxidative phosphorylation profiles, but are nonetheless sensitive to inhibitors of the electron transport chain, which supports clinical recommendations that individuals with Costeff Syndrome avoid mitochondria-damaging agents. In summary, this paper introduces a faithful Costeff Syndrome model and demonstrates a requirement for mitochondrial OPA3 to limit HMG-CoA-derived MGC and protect the electron transport chain against inhibitory compounds.
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Registered trials
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.