ArticlePLoS genetics2013
Aconitase causes iron toxicity in Drosophila pink1 mutants.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Rethinking 'rare'Journal of Parkinson's disease · 2025Pooled it
- Infantile Cerebellar-Retinal Degeneration Associated With Novel ACO2 Variants: Clinical Features and Insights From a Drosophila Model.Clinical genetics · 2025Article
- Ferroptosis: iron release mechanisms in the bioenergetic process.Cancer metastasis reviews · 2025Review
- Binding of α-synuclein to ACO2 promotes progressive mitochondrial dysfunction in Parkinson's disease models.Redox biology · 2024Article
- Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Iron-sulfur cluster loss in mitochondrial CISD1 mediates PINK1 loss-of-function phenotypes.eLife · 2024Article
- Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.Nature communications · 2024Article
- Mitochondrial Differentiation during Spermatogenesis: Lessons fromInternational journal of molecular sciences · 2024Review
- ACO2 deficiency increases vulnerability to Parkinson's disease via dysregulating mitochondrial function and histone acetylation-mediated transcription of autophagy genes.Communications biology · 2023Article
- A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels.Nature metabolism · 2023Article
- How the Disruption of Mitochondrial Redox Signalling Contributes to Ageing.Antioxidants (Basel, Switzerland) · 2023Review
- Sphingolipids in neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- Nitric Oxide Negatively Regulates the Rapid Formation ofJournal of fungi (Basel, Switzerland) · 2022Article
- Mitochondrial aconitase 1 regulates age-related memory impairment via autophagy/mitophagy-mediated neural plasticity in middle-aged flies.Aging cell · 2021Article
- Calcium chelator BAPTA‑AM protects against iron overload‑induced chondrocyte mitochondrial dysfunction and cartilage degeneration.International journal of molecular medicine · 2021Article
- The Importance ofCells · 2021Review
- Human Dopaminergic Neurons Lacking PINK1 Exhibit Disrupted Dopamine Metabolism Related to Vitamin B6 Co-Factors.iScience · 2020Article
- Article
- Review
- Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer.Redox biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase, and pink1 mutations cause early onset Parkinson's disease (PD) in humans. Loss of pink1 in Drosophila leads to defects in mitochondrial function, and genetic data suggest that another PD-related gene product, Parkin, acts with pink1 to regulate the clearance of dysfunctional mitochondria (mitophagy). Consequently, pink1 mutants show an accumulation of morphologically abnormal mitochondria, but it is unclear if other factors are involved in pink1 function in vivo and contribute to the mitochondrial morphological defects seen in specific cell types in pink1 mutants. To explore the molecular mechanisms of pink1 function, we performed a genetic modifier screen in Drosophila and identified aconitase (acon) as a dominant suppressor of pink1. Acon localizes to mitochondria and harbors a labile iron-sulfur [4Fe-4S] cluster that can scavenge superoxide to release hydrogen peroxide and iron that combine to produce hydroxyl radicals. Using Acon enzymatic mutants, and expression of mitoferritin that scavenges free iron, we show that [4Fe-4S] cluster inactivation, as a result of increased superoxide in pink1 mutants, results in oxidative stress and mitochondrial swelling. We show that [4Fe-4S] inactivation acts downstream of pink1 in a pathway that affects mitochondrial morphology, but acts independently of parkin. Thus our data indicate that superoxide-dependent [4Fe-4S] inactivation defines a potential pathogenic cascade that acts independent of mitophagy and links iron toxicity to mitochondrial failure in a PD-relevant model.
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Registered trials
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