ArticleThe Journal of biological chemistry2011
Elevated CO(2) levels cause mitochondrial dysfunction and impair cell proliferation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 173 citations in OpenAlex.
- The Relationship between Resistance Exercise Performance and Ventilatory Efficiency after Beetroot Juice Intake in Well-Trained Athletes.Nutrients · 2021Trial
- Hypercapnia enhances airway smooth muscle contractility via STIM1-dependent Ca2+ signaling.JCI insight · 2026Article
- Autophagic flux blockade under hypocapnia reveals CO2-sensitive regulation of autophagy-lysosome homeostasis.Biology open · 2026Article
- Computational design of artificial supply networks for engineered human tissue.Scientific reports · 2026Article
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- Long-term DNA methylation changes induced by age and elevated COSkeletal muscle · 2025Article
- Pseudopregnancy in dromedary camels: hematological and biochemical profiles and therapeutic responses.Tropical animal health and production · 2025Article
- Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review.International journal of molecular sciences · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Bioenergetics and metabolism of the pulmonary endothelium. Scientific session I: ReSPIRE 2025.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Gene Expression Profiling of Pancreatic Ductal Adenocarcinoma Cells in Hypercapnia Identifies SIAH3 as a Novel Prognostic Biomarker.International journal of molecular sciences · 2025Article
- Proteomic analysis of premature umbilical cord blood and its relationship with bronchopulmonary dysplasia.Italian journal of pediatrics · 2025Observational
- Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.JCI insight · 2025Article
- Investigating the Underlying Mechanisms of Ma-Xing-Shi-Gan-Tang on Asthma via Metabolomics and Network Pharmacology.Journal of inflammation research · 2025Article
- Exposure of Primary Human Skin Fibroblasts to Carbon Dioxide-Containing Solution Significantly Reduces TGF-β-Induced Myofibroblast Differentiation In Vitro.International journal of molecular sciences · 2024Article
- Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.PloS one · 2024Article
- Lowering PRespiratory care · 2023Article
- Integrated small RNA, mRNA and protein omics reveal a miRNA network orchestrating metabolic maturation of the developing human heart.BMC genomics · 2023Article
- Loss of ANT1 Increases Fibrosis and Epithelial Cell Senescence in Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2023Article
- Carbon dioxide regulates cholesterol levels through SREBP2.PLoS biology · 2023Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Elevated CO(2) concentrations (hypercapnia) occur in patients with severe lung diseases. Here, we provide evidence that high CO(2) levels decrease O(2) consumption and ATP production and impair cell proliferation independently of acidosis and hypoxia in fibroblasts (N12) and alveolar epithelial cells (A549). Cells exposed to elevated CO(2) died in galactose medium as well as when glucose-6-phosphate isomerase was knocked down, suggesting mitochondrial dysfunction. High CO(2) levels led to increased levels of microRNA-183 (miR-183), which in turn decreased expression of IDH2 (isocitrate dehydrogenase 2). The high CO(2)-induced decrease in cell proliferation was rescued by α-ketoglutarate and overexpression of IDH2, whereas proliferation decreased in normocapnic cells transfected with siRNA for IDH2. Also, overexpression of miR-183 decreased IDH2 (mRNA and protein) as well as cell proliferation under normocapnic conditions, whereas inhibition of miR-183 rescued the normal proliferation phenotype in cells exposed to elevated levels of CO(2). Accordingly, we provide evidence that high CO(2) induces miR-183, which down-regulates IDH2, thus impairing mitochondrial function and cell proliferation. These results are of relevance to patients with hypercapnia such as those with chronic obstructive pulmonary disease, asthma, cystic fibrosis, bronchopulmonary dysplasia, and muscular dystrophies.
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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.