Isolated Cytochrome c Oxidase Deficiency in G93A SOD1 Mice Overexpressing CCS Protein
| Autor: | Ronald G. Haller, Scot C. Leary, Jeffrey L. Elliott, Nadine Romain, Marjatta Son, Dennis R. Winge, Fabien Pierrel |
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| Přispěvatelé: | Department of Neurology, University of Texas Southwestern, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Institute for Exercise and Environmental Medicine, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Utah |
| Rok vydání: | 2008 |
| Předmět: |
animal diseases
Cytochrome-c Oxidase Deficiency Kidney Biochemistry Oxidative Phosphorylation MESH: Spinal Cord Mice chemistry.chemical_compound 0302 clinical medicine MESH: Animals MESH: Organ Specificity MESH: Superoxide Dismutase 0303 health sciences Alanine MESH: Protein Subunits MESH: Amino Acid Substitution MESH: Glycine Metabolism and Bioenergetics Mitochondrial respiratory chain medicine.anatomical_structure Spinal Cord Organ Specificity MESH: Heme Electrophoresis Polyacrylamide Gel MESH: Molecular Chaperones Genetically modified mouse MESH: Alanine MESH: Mice Transgenic Protein subunit SOD1 Glycine Mice Transgenic Heme Oxidative phosphorylation Biology 03 medical and health sciences MESH: Oxidative Phosphorylation medicine Animals Humans Cytochrome c oxidase [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice Molecular Biology MESH: Cytochrome-c Oxidase Deficiency 030304 developmental biology MESH: Humans Superoxide Dismutase fungi nutritional and metabolic diseases MESH: Kidney Cell Biology Spinal cord Molecular biology nervous system diseases Protein Subunits Heme A Amino Acid Substitution nervous system chemistry biology.protein 030217 neurology & neurosurgery MESH: Electrophoresis Polyacrylamide Gel Molecular Chaperones |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (18), pp.12267-75. ⟨10.1074/jbc.M708523200⟩ Journal of Biological Chemistry, 2008, 283 (18), pp.12267-75. ⟨10.1074/jbc.M708523200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.m708523200 |
| Popis: | International audience; G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy. |
| Databáze: | OpenAIRE |
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