ArticleAmerican journal of respiratory and critical care medicine2013
Superoxide generated at mitochondrial complex III triggers acute responses to hypoxia in the pulmonary circulation.
Article in American journal of respiratory and critical care medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
94 citing papers in PubMed, 152 citations in OpenAlex.
- Pulmonary vascular dysfunction in ARDS Pathophysiology and therapeutic implications.Annals of intensive care · 2026Review
- A guide to reactive oxygen species in tumour hypoxia: measurement and therapeutic implications.Molecular oncology · 2025Review
- Treg activation during allograft tolerance induction requires mitochondrion-induced TGF-β1 in type 1 conventional dendritic cells.The Journal of clinical investigation · 2025Article
- Mitochondrial respiration is necessary for CD8Nature immunology · 2025Article
- Prokaryotic organelle mitochondria drive tumorigenesis: "the original sin".Frontiers in oncology · 2025Review
- Article
- Revisiting reactive oxygen species production in hypoxia.Pflugers Archiv : European journal of physiology · 2024Review
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis.International journal of molecular sciences · 2024Article
- Rieske Iron-Sulfur Protein Mediates Pulmonary Hypertension Following Nicotine/Hypoxia Coexposure.American journal of respiratory cell and molecular biology · 2024Article
- Cancer Metabolism under Limiting Oxygen Conditions.Cold Spring Harbor perspectives in medicine · 2024Review
- Oxidative stress in acute pulmonary embolism: emerging roles and therapeutic implications.Thrombosis journal · 2024Review
- RCCD1 promotes breast carcinogenesis through regulating hypoxia-associated mitochondrial homeostasis.Oncogene · 2023Article
- Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2023Article
- How the Disruption of Mitochondrial Redox Signalling Contributes to Ageing.Antioxidants (Basel, Switzerland) · 2023Review
- Role of ryanodine receptor 2 and FK506-binding protein 12.6 dissociation in pulmonary hypertension.The Journal of general physiology · 2023Article
- Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets.Frontiers in physiology · 2023Review
- Acute oxygen sensing by vascular smooth muscle cells.Frontiers in physiology · 2023Review
- Adult-Onset Deficiency of Mitochondrial Complex III in a Mouse Model of Alzheimer's Disease Decreases Amyloid Beta Plaque Formation.Molecular neurobiology · 2022Article
- Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleThe role of reactive oxygen species (ROS) signaling in the O(2) sensing mechanism underlying acute hypoxic pulmonary vasoconstriction (HPV) has been controversial. Although mitochondria are important sources of ROS, studies using chemical inhibitors have yielded conflicting results, whereas cellular models using genetic suppression have precluded in vivo confirmation. Hence, genetic animal models are required to test mechanistic hypotheses.
objectivesWe tested whether mitochondrial Complex III is required for the ROS signaling and vasoconstriction responses to acute hypoxia in pulmonary arteries (PA).
methodsA mouse permitting Cre-mediated conditional deletion of the Rieske iron-sulfur protein (RISP) of Complex III was generated. Adenoviral Cre recombinase was used to delete RISP from isolated PA vessels or smooth muscle cells (PASMC). MEASUREMENTS AND MAIN
resultsIn PASMC, RISP depletion abolished hypoxia-induced increases in ROS signaling in the mitochondrial intermembrane space and cytosol, and it abrogated hypoxia-induced increases in [Ca(2+)](i). In isolated PA vessels, RISP depletion abolished hypoxia-induced ROS signaling in the cytosol. Breeding the RISP mice with transgenic mice expressing tamoxifen-activated Cre in smooth muscle permitted the depletion of RISP in PASMC in vivo. Precision-cut lung slices from those mice revealed that RISP depletion abolished hypoxia-induced increases in [Ca(2+)](i) of the PA. In vivo RISP depletion in smooth muscle attenuated the acute hypoxia-induced increase in right ventricular systolic pressure in anesthetized mice.
conclusionsAcute hypoxia induces superoxide release from Complex III of smooth muscle cells. These oxidant signals diffuse into the cytosol and trigger increases in [Ca(2+)](i) that cause acute hypoxic pulmonary vasoconstriction.
Indexed as
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.