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Essential Role of Mitochondrial Cytochrome c Oxidase Subunit 4 Isoform 2 (Cox4i2) for Acute Pulmonary Oxygen Sensing

Giordano, Luca (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
Nolte, Anika (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
Wittig, Ilka (författare)
Faculty of Medicine Goethe-University Frankfurt, Germany
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Pak, Oleg (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
Knoepp, Fenja (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
Ramser, Kerstin (författare)
Luleå tekniska universitet,Strömningslära och experimentell mekanik
Wahl, Joel (författare)
Luleå tekniska universitet,Strömningslära och experimentell mekanik
Huettemann, Maik (författare)
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, USA
Grossman, Lawrence I. (författare)
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, USA
Pecina, Petr (författare)
Laboratory of Bioenergetics, Institute of Physiology CAS, Prague, Czech Republic
Ghofrani, Hossein A. (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
Seeger, Werner (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany; Institute for Lung Health, Justus-Liebig University, Giessen, Germany
Weissmann, Norbert (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
Giehl, Klaudia (författare)
Department of Internal Medicine, Justus-Liebig University, Giessen, Germany
Sommer, Natascha (författare)
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute, Justus-Liebig University, Giessen, Germany
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 (creator_code:org_t)
Elsevier, 2022
2022
Engelska.
Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier. - 0005-2728 .- 1879-2650. ; 1863:Supplement
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Mitochondrial Cytochrome c Oxidase Subunit 4 Isoform 2 (Cox4i2) is essential for acute oxygen sensing and signaling in pulmonary arterial smooth muscle cells (PASMCs) by triggering the production of superoxide during acute hypoxia [1]. However, the molecular mechanism underlying Cox4i2-dependent oxygen sensing remains elusive. We analysed oxygen-dependent respiration by high resolution respirometry, redox changes of the electron transport chain (ETC) by RAMAN spectroscopy, and supercomplex formation by blue native gel analysis of PASMCs isolated from wild type (WT) and Cox4i2-/- mice. To understand the role of Cox4i2-specific cysteine residues we determined hypoxia-induced superoxide production and oxygen affinity in a mouse epithelial cell line (CMT167 cells) overexpressing either Cox4i1, or WT Cox4i2, or Cox4i2 mutants (C41S, C55A, C109S). Respiration and supercomplex formation were similar in WT and Cox4i2-/- PASMCs. Interestingly, hypoxia-induced reduction of ETC components (NADH, ubiquinol, and reduced cytochrome c) was prevented in Cox4i2-/- PASMCs. CMT167 cells expressing either Cox4i1, or Cox4i2 mutants lacked hypoxia-induced superoxide release, which was detected only in cells expressing WT Cox4i2. In contrast, overexpression of Cox4i1, or Cox4i2, or Cox4i2 mutants did not affect oxygen affinity. Our findings suggest that Cox4i2 does not alter superoxide production by rearrangement of supercomplexes, whereas its specific cysteines are needed for the superoxide release. In conclusion, Cox4i2 plays a major role in the hypoxia-induced reduction of ETC components, likely mediated through its redox-active cysteine residues.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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