ArticleScience advances2020
Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The trial behind it
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Lactylation at the metabolic-epigenetic interface in cardiovascular diseases: context-dependent mechanisms and translational roadmap.Journal of advanced research · 2026Review
- Mitochondrial electron transport chain is essential for acute inflammatory stress responses in mouse fibroblasts.Scientific reports · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Hypoxic Pulmonary Hypertension: Molecular Mechanisms and Clinical Research Advances.International journal of molecular sciences · 2026Review
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology.Nature metabolism · 2025Article
- Mitochondrial respiration is necessary for CD8Nature immunology · 2025Article
- HInternational journal of molecular sciences · 2025Article
- Image-guided targeting of mitochondrial metabolism sensitizes pediatric malignant rhabdoid tumors to low-dose radiotherapy.Science advances · 2025Article
- Piezo1 in PASMCs: Critical for Hypoxia-Induced Pulmonary Hypertension Development.Circulation research · 2025Article
- Neurocardiology: translational advancements and potential.The Journal of physiology · 2025Review
- Mitochondria complex III-generated superoxide is essential for IL-10 secretion in macrophages.Science advances · 2025Article
- Lactylation in Tumor Immune Escape and Immunotherapy: Multifaceted Functions and Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- Revisiting reactive oxygen species production in hypoxia.Pflugers Archiv : European journal of physiology · 2024Review
- The physiological basis for individualized oxygenation targets in critically ill patients with circulatory shock.Intensive care medicine experimental · 2024Review
- Use of FRET-Sensor 'Mermaid' to Detect Subtle Changes in Membrane Potential of Primary Mouse PASMCs.Cells · 2024Article
- Alternative oxidase blunts pseudohypoxia and photoreceptor degeneration due to RPE mitochondrial dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hyperbaric oxygen treatment reveals spatiotemporal OXPHOS plasticity in the porcine heart.PNAS nexus · 2024Article
- Review
- New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- From Beach to the Bedside: Harnessing Mitochondrial Function in Human Diseases Using New Marine-Derived Strategies.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondria play an important role in sensing both acute and chronic hypoxia in the pulmonary vasculature, but their primary oxygen-sensing mechanism and contribution to stabilization of the hypoxia-inducible factor (HIF) remains elusive. Alteration of the mitochondrial electron flux and increased superoxide release from complex III has been proposed as an essential trigger for hypoxic pulmonary vasoconstriction (HPV). We used mice expressing a tunicate alternative oxidase, AOX, which maintains electron flux when respiratory complexes III and/or IV are inhibited. Respiratory restoration by AOX prevented acute HPV and hypoxic responses of pulmonary arterial smooth muscle cells (PASMC), acute hypoxia-induced redox changes of NADH and cytochrome c, and superoxide production. In contrast, AOX did not affect the development of chronic hypoxia-induced pulmonary hypertension and HIF-1α stabilization. These results indicate that distal inhibition of the mitochondrial electron transport chain in PASMC is an essential initial step for acute but not chronic oxygen sensing.
Identifiers
What OpenQuestion holds
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.