ArticlePloS one2012
Modeling pathogenic mutations of human twinkle in Drosophila suggests an apoptosis role in response to mitochondrial defects.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Impairment of Muscle Function Causes Pupal Lethality in Flies Expressing the Mitochondrial Alternative Oxidase.Biomolecules · 2025Article
- Experimental horizontal transfer of phage-derived genes to Drosophila confers innate immunity to parasitoids.Current biology : CB · 2025Article
- Article
- Dysfunction of Drosophila mitochondrial carrier homolog (Mtch) alters apoptosis and disturbs development.FEBS open bio · 2024Article
- Mitochondrial Neurodegeneration: Lessons fromBiomolecules · 2023Review
- Ginsenoside Rg1 Delays Chronological Aging in a Yeast Model via CDC19- and SDH2-Mediated Cellular Metabolism.Antioxidants (Basel, Switzerland) · 2023Article
- Mitochondrial DNA maintenance in Drosophila melanogaster.Bioscience reports · 2022Review
- Insights regarding mitochondrial DNA copy number alterations in human cancer (Review).International journal of molecular medicine · 2022Review
- Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase.Scientific reports · 2018Article
- Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase.Nucleic acids research · 2018Article
- Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria.Nature communications · 2018Article
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
- Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases.Ageing research reviews · 2017Review
- Structure, function and evolution of the animal mitochondrial replicative DNA helicase.Critical reviews in biochemistry and molecular biology · 2016Review
- Purification and Comparative Assay of the Human Mitochondrial Replicative DNA Helicase.Methods in molecular biology (Clifton, N.J.) · 2016Article
- SUV3 helicase is required for correct processing of mitochondrial transcripts.Nucleic acids research · 2015Article
- The N-terminal domain of the Drosophila mitochondrial replicative DNA helicase contains an iron-sulfur cluster and binds DNA.The Journal of biological chemistry · 2014Article
- Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy.Neurogenetics · 2014Article
- Invertebrate models for coenzyme q10 deficiency.Molecular syndromology · 2014Article
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
The human gene C10orf2 encodes the mitochondrial replicative DNA helicase Twinkle, mutations of which are responsible for a significant fraction of cases of autosomal dominant progressive external ophthalmoplegia (adPEO), a human mitochondrial disease caused by defects in intergenomic communication. We report the analysis of orthologous mutations in the Drosophila melanogaster mitochondrial DNA (mtDNA) helicase gene, d-mtDNA helicase. Increased expression of wild type d-mtDNA helicase using the UAS-GAL4 system leads to an increase in mtDNA copy number throughout adult life without any noteworthy phenotype, whereas overexpression of d-mtDNA helicase containing the K388A mutation in the helicase active site results in a severe depletion of mtDNA and a lethal phenotype. Overexpression of two d-mtDNA helicase variants equivalent to two human adPEO mutations shows differential effects. The A442P mutation exhibits a dominant negative effect similar to that of the active site mutant. In contrast, overexpression of d-mtDNA helicase containing the W441C mutation results in a slight decrease in mtDNA copy number during the third instar larval stage, and a moderate decrease in life span in the adult population. Overexpression of d-mtDNA helicase containing either the K388A or A442P mutations causes a mitochondrial oxidative phosphorylation (OXPHOS) defect that significantly reduces cell proliferation. The mitochondrial impairment caused by these mutations promotes apoptosis, arguing that mitochondria regulate programmed cell death in Drosophila. Our study of d-mtDNA helicase overexpression provides a tractable Drosophila model for understanding the cellular and molecular effects of human adPEO mutations.
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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.