ArticleHuman molecular genetics2015
Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Spatial mapping of CoQ10 repletion by BPM31510 in a genetic mouse model (Coq4Journal of lipid research · 2026Article
- Induced pluripotent stem cells carrying novel APTX mutations presented defective neural differentiation with the accumulation of DNA single-strand breaks.Cell death discovery · 2025Article
- Coenzyme QFree radical biology & medicine · 2025Article
- Understanding coenzyme Q.Physiological reviews · 2024Review
- Mechanisms and Therapeutic Effects of Benzoquinone Ring Analogs in Primary CoQ Deficiencies.Antioxidants (Basel, Switzerland) · 2022Review
- Mitochondrial Neurodegeneration.Cells · 2022Review
- Chemical Inhibition of Apurinic-Apyrimidinic Endonuclease 1 Redox and DNA Repair Functions Affects the Inflammatory Response via Different but Overlapping Mechanisms.Frontiers in cell and developmental biology · 2021Article
- Article
- Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress.Oxidative medicine and cellular longevity · 2020Article
- The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force.Cerebellum (London, England) · 2019Review
- Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias.Current neuropharmacology · 2019Review
- Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes.Journal of anesthesia · 2018Article
- Molecular Signaling in Response to Charged Particle Exposures and its Importance in Particle Therapy.International journal of particle therapy · 2018Review
- Complementation of aprataxin deficiency by base excision repair enzymes in mitochondrial extracts.Nucleic acids research · 2017Article
- Neurological disorders associated with DNA strand-break processing enzymes.Mechanisms of ageing and development · 2017Review
- Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.Scientific reports · 2015Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized to mitochondria in neuroblastoma cells, where it enhances preservation of mitochondrial function. In this study, we show that aprataxin deficiency impairs mitochondrial function, independent of its role in mitochondrial DNA repair. The bioenergetics defect in AOA1-mutant fibroblasts and APTX-depleted Hela cells is caused by decreased expression of SDHA and genes encoding CoQ biosynthetic enzymes, in association with reductions of APE1, NRF1 and NRF2. The biochemical and molecular abnormalities in APTX-depleted cells are recapitulated by knockdown of APE1 in Hela cells and are rescued by overexpression of NRF1/2. Importantly, pharmacological upregulation of NRF1 alone by 5-aminoimidazone-4-carboxamide ribonucleotide does not rescue the phenotype, which, in contrast, is reversed by the upregulation of NRF2 by rosiglitazone. Accordingly, we propose that the lack of aprataxin causes reduction of the pathway APE1/NRF1/NRF2 and their target genes. Our findings demonstrate a critical role of APTX in transcription regulation of mitochondrial function and the pathogenesis of AOA1 via a novel pathomechanistic pathway, which may be relevant to other neurodegenerative diseases.
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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.