ArticleThe Journal of biological chemistry2014
Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Unraveling the molecular landscape and therapeutic strategies for acute kidney injury: insights from transcriptomics, network pharmacology, virtual screening, and in vitro experiments.Molecular diversity · 2026Article
- Mitochondrial protein-enriched artificial nanovesicles: mitochondrial recovery and antioxidation for diabetic wound treatment.Journal of nanobiotechnology · 2026Article
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Critical role of mitochondrial aconitase in skeletal muscle maturation.Scientific reports · 2025Article
- Cell-Free Circulating Mitochondrial DNA Levels Following High-Frequency Jet Ventilation-A Post Hoc Analysis.Journal of clinical medicine · 2025Article
- Unveiling the vital role of OGG1 in inflammation, vascular endothelial damage, and cell death in obstetric and gynecological diseases.Human cell · 2025Review
- Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell.Advanced biology · 2025Review
- Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Potential New Target for Dry Eye Disease-Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Review
- 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) alleviates lung injury by inhibiting SIRT6-HIF-1α signaling pathway activation through the upregulation of miR-212-5p expression.Molecular biology reports · 2024Article
- Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response.Nature communications · 2023Article
- OGG1 inhibition suppresses African swine fever virus replication.Virologica Sinica · 2023Article
- Oxygen toxicity: cellular mechanisms in normobaric hyperoxia.Cell biology and toxicology · 2023Review
- Nuclear Receptor NR1D1 Regulates Abdominal Aortic Aneurysm Development by Targeting the Mitochondrial Tricarboxylic Acid Cycle Enzyme Aconitase-2.Circulation · 2022Article
- The Role of Sphingolipid Signaling in Oxidative Lung Injury and Pathogenesis of Bronchopulmonary Dysplasia.International journal of molecular sciences · 2022Review
- OGG1 in the Kidney: Beyond Base Excision Repair.Oxidative medicine and cellular longevity · 2022Review
- Dynamic immune response characteristics of piglets infected with Actinobacillus pleuropneumoniae through omic.AMB Express · 2021Article
- SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment.International journal of molecular sciences · 2021Article
- Chelerythrine Ameliorates Pulmonary Fibrosis via Activating the Nrf2/ARE Signaling Pathway.Cell biochemistry and biophysics · 2021Article
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Abstract
Mitochondria-targeted human 8-oxoguanine DNA glycosylase (mt-hOgg1) and aconitase-2 (Aco-2) each reduce oxidant-induced alveolar epithelial cell (AEC) apoptosis, but it is unclear whether protection occurs by preventing AEC mitochondrial DNA (mtDNA) damage. Using quantitative PCR-based measurements of mitochondrial and nuclear DNA damage, mtDNA damage was preferentially noted in AEC after exposure to oxidative stress (e.g. amosite asbestos (5-25 μg/cm(2)) or H2O2 (100-250 μM)) for 24 h. Overexpression of wild-type mt-hOgg1 or mt-long α/β 317-323 hOgg1 mutant incapable of DNA repair (mt-hOgg1-Mut) each blocked A549 cell oxidant-induced mtDNA damage, mitochondrial p53 translocation, and intrinsic apoptosis as assessed by DNA fragmentation and cleaved caspase-9. In contrast, compared with controls, knockdown of Ogg1 (using Ogg1 shRNA in A549 cells or primary alveolar type 2 cells from ogg1(-/-) mice) augmented mtDNA lesions and intrinsic apoptosis at base line, and these effects were increased further after exposure to oxidative stress. Notably, overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis, whereas siRNA for Aco-2 (siAco-2) enhanced mtDNA damage, mitochondrial p53 translocation, and apoptosis. Finally, siAco-2 attenuated the protective effects of mt-hOgg1-Mut but not wild-type mt-hOgg1 against oxidant-induced mtDNA damage and apoptosis. Collectively, these data demonstrate a novel role for mt-hOgg1 and Aco-2 in preserving AEC mtDNA integrity, thereby preventing oxidant-induced mitochondrial dysfunction, p53 mitochondrial translocation, and intrinsic apoptosis. Furthermore, mt-hOgg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity.
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