ArticleCirculation research2017
Mitochondrial Complex IV Subunit 4 Isoform 2 Is Essential for Acute Pulmonary Oxygen Sensing.
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Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed, 116 citations in OpenAlex.
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5 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 1 institution in 1 country.
Natascha SommerFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Maik HüttemannFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Oleg PakFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Susan ScheibeFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Fenja KnoeppFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Christopher SinklerFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Monika MalczykFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Mareike GierhardtFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Azadeh EsfandiaryFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Simone KrautFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Felix JonasFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Christine VeithFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Siddhesh ArasFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Akylbek SydykovFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Nasim AlebrahimdehkordiFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Klaudia GiehlFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Matthias HeckerFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Ralf P BrandesFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Werner SeegerFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Friedrich GrimmingerFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Hossein A GhofraniFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Ralph T SchermulyFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Lawrence I GrossmanFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.). lgrossman@wayne.edu Norbert.Weissmann@innere.med.uni-giessen.de.
Norbert WeissmannFrom the Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany (N.S., O.P., S.S., F.K., M.M., M.G., A.E., S.K., F.J., C.V., A.S., N.A., K.G., M.H., W.S., F.G., H.A.G., R.T.S., N.W.); Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.H., C.S., S.A., L.I.G.); Institut für Kardiovaskuläre Physiologie, Goethe-Universität, German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany (R.P.B.); and Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (W.S.).
Wayne State University · US
Funding
MOLECULAR GENETICS OF MAMMALIAN CYTOCHROME OXIDASER01GM048517 · NIGMS · WAYNE STATE UNIVERSITY · PI GROSSMAN, LAWRENCE · 1993 to 2001
$417kNIGMS NIH HHS R01 GM048517
Abstract
rationaleAcute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as a critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and the mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing, remain unresolved.
objectivesTo investigate the role of the pulmonary-specific isoform 2 of subunit 4 of the mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling. METHODS AND
resultsIsolated ventilated and perfused lungs from
conclusionsCox4i2 is essential for acute but not chronic pulmonary oxygen sensing by triggering mitochondrial hyperpolarization and release of mitochondrial superoxide which, after conversion to hydrogen peroxide, contributes to cellular membrane depolarization and HPV. These findings provide a new model for oxygen-sensing processes in the lung and possibly also in other organs.
Indexed as
AnimalsCell HypoxiaCell Line, TumorElectron Transport Complex IVFemaleHumansLungMaleMembrane Potential, MitochondrialMiceMice, KnockoutMitochondriaOxygenCOX4I2 protein, humanElectron Transport Complex IVOxygenelectron transport complex IVhypoxiamitochondriapotassium channelspulmonary circulationreactive oxygen species
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