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Essential Role of M...
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Giordano, LucaDepartment 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
(författare)
Essential Role of Mitochondrial Cytochrome c Oxidase Subunit 4 Isoform 2 (Cox4i2) for Acute Pulmonary Oxygen Sensing
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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Elsevier,2022
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Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:ltu-93350
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https://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-93350URI
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https://doi.org/10.1016/j.bbabio.2022.148893DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Godkänd;2022;Nivå 0;2022-10-05 (hanlid);Konferensartikel i tidskrift;Funder: DFG, German Research Foundation (268555672 – SFB 1213)Part of special issue: EBEC2022, the 21st European Bioenergetics Conference, Aix-en-Provence, France, August 20-25, 2022, Abstract Book
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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.
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Nolte, AnikaDepartment 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
(författare)
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Wittig, IlkaFaculty of Medicine Goethe-University Frankfurt, Germany
(författare)
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Pak, OlegDepartment 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
(författare)
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Knoepp, FenjaDepartment 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
(författare)
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Ramser, KerstinLuleå tekniska universitet,Strömningslära och experimentell mekanik(Swepub:ltu)ramser
(författare)
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Wahl, JoelLuleå tekniska universitet,Strömningslära och experimentell mekanik(Swepub:ltu)joewah
(författare)
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Huettemann, MaikCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, USA
(författare)
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Grossman, Lawrence I.Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, USA
(författare)
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Pecina, PetrLaboratory of Bioenergetics, Institute of Physiology CAS, Prague, Czech Republic
(författare)
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Ghofrani, Hossein A.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
(författare)
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Seeger, WernerDepartment 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
(författare)
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Weissmann, NorbertDepartment 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
(författare)
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Giehl, KlaudiaDepartment of Internal Medicine, Justus-Liebig University, Giessen, Germany
(författare)
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Sommer, NataschaDepartment 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
(författare)
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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, GermanyFaculty of Medicine Goethe-University Frankfurt, Germany
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Biochimica et Biophysica Acta - Bioenergetics: Elsevier1863:Supplement0005-27281879-2650
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Giordano, Luca
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Nolte, Anika
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Wittig, Ilka
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Pak, Oleg
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Knoepp, Fenja
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Ramser, Kerstin
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visa fler...
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Wahl, Joel
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Huettemann, Maik
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Grossman, Lawren ...
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Pecina, Petr
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Ghofrani, Hossei ...
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Seeger, Werner
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Weissmann, Norbe ...
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Giehl, Klaudia
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Sommer, Natascha
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