ArticleArteriosclerosis, thrombosis, and vascular biology2018
Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Computational modeling of substrate-dependent lung mitochondrial respiration and bioenergetics in rats with different susceptibility to hyperoxia-induced ARDS.American journal of physiology. Cell physiology · 2026Article
- Hyperoxia and iron homeostasis in developing human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Sex-specific differences in lung mitochondrial function and injury in rats exposed to hyperoxia.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- Peroxisome Proliferator-Activated Receptor α Deficiency Induces Vascular Pathologies through Endothelial Senescence in Diabetic Retinopathy.The American journal of pathology · 2026Article
- Cell-Free Circulating Mitochondrial DNA Levels Following High-Frequency Jet Ventilation-A Post Hoc Analysis.Journal of clinical medicine · 2025Article
- Ferroptosis and hyperoxic lung injury: insights into pathophysiology and treatment approaches.Frontiers in pharmacology · 2025Review
- Caffeine, MitoQ, and GABA Prophylaxis of Mitochondrial Dysfunction Induced in Human Pulmonary Cells by Normobaric-Hyperoxia and Hyperbaric-Hyperoxia.Oxidative medicine and cellular longevity · 2025Article
- Mitochondria as the central regulator of cell death in bronchopulmonary dysplasia.Frontiers in physiology · 2025Review
- Activated DRP1 promotes mitochondrial fission and induces glycolysis in ATII cells under hyperoxia.Respiratory research · 2024Article
- Injectable, oxygen-releasing, thermosensitive hydrogel promotes vascularized bone formation with prolonged oxygen delivery and improved osteoinductivity.Materials today. Bio · 2024Article
- Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.American journal of respiratory cell and molecular biology · 2024Article
- [Role of reactive oxygen species/silent information regulator 1 in hyperoxia-induced bronchial epithelial cell injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
- Article
- Post-translational modifications and bronchopulmonary dysplasia.Frontiers in pediatrics · 2024Review
- Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.Nature reviews. Cardiology · 2023Review
- Genetically Encoded Biosensors for the Fluorescence Detection of OSensors (Basel, Switzerland) · 2023Review
- Article
- Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate ischemic injury.Acta biomaterialia · 2023Article
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveWe explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. APPROACH AND
resultsMitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter-binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1.
conclusionsBecause hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction.
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