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Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol

Superoxide dismutase 1 (Sod1) is an important antioxidative enzyme that converts superoxide anions to hydrogen peroxide and water. Active Sod1 is a homodimer containing one zinc ion, one copper ion, and one disulfide bond per subunit. Maturation of Sod1 depends on its copper chaperone (Ccs1). Sod1 a...

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Autores principales: Klöppel, Christine, Suzuki, Yutaka, Kojer, Kerstin, Petrungaro, Carmelina, Longen, Sebastian, Fiedler, Sebastian, Keller, Sandro, Riemer, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192855/
https://www.ncbi.nlm.nih.gov/pubmed/21865594
http://dx.doi.org/10.1091/mbc.E11-04-0293
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author Klöppel, Christine
Suzuki, Yutaka
Kojer, Kerstin
Petrungaro, Carmelina
Longen, Sebastian
Fiedler, Sebastian
Keller, Sandro
Riemer, Jan
author_facet Klöppel, Christine
Suzuki, Yutaka
Kojer, Kerstin
Petrungaro, Carmelina
Longen, Sebastian
Fiedler, Sebastian
Keller, Sandro
Riemer, Jan
author_sort Klöppel, Christine
collection PubMed
description Superoxide dismutase 1 (Sod1) is an important antioxidative enzyme that converts superoxide anions to hydrogen peroxide and water. Active Sod1 is a homodimer containing one zinc ion, one copper ion, and one disulfide bond per subunit. Maturation of Sod1 depends on its copper chaperone (Ccs1). Sod1 and Ccs1 are dually localized proteins that reside in the cytosol and in the intermembrane space of mitochondria. The import of Ccs1 into mitochondria depends on the mitochondrial disulfide relay system. However, the exact mechanism of this import process has been unclear. In this study we detail the import and folding pathway of Ccs1 and characterize its interaction with the oxidoreductase of the mitochondrial disulfide relay Mia40. We identify cysteines at positions 27 and 64 in domain I of Ccs1 as critical for mitochondrial import and interaction with Mia40. On interaction with Mia40, these cysteines form a structural disulfide bond that stabilizes the overall fold of domain I. Although the cysteines are essential for the accumulation of functional Ccs1 in mitochondria, they are dispensable for the enzymatic activity of cytosolic Ccs1. We propose a model in which the Mia40-mediated oxidative folding of domain I controls the cellular distribution of Ccs1 and, consequently, active Sod1.
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spelling pubmed-31928552011-12-30 Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol Klöppel, Christine Suzuki, Yutaka Kojer, Kerstin Petrungaro, Carmelina Longen, Sebastian Fiedler, Sebastian Keller, Sandro Riemer, Jan Mol Biol Cell Articles Superoxide dismutase 1 (Sod1) is an important antioxidative enzyme that converts superoxide anions to hydrogen peroxide and water. Active Sod1 is a homodimer containing one zinc ion, one copper ion, and one disulfide bond per subunit. Maturation of Sod1 depends on its copper chaperone (Ccs1). Sod1 and Ccs1 are dually localized proteins that reside in the cytosol and in the intermembrane space of mitochondria. The import of Ccs1 into mitochondria depends on the mitochondrial disulfide relay system. However, the exact mechanism of this import process has been unclear. In this study we detail the import and folding pathway of Ccs1 and characterize its interaction with the oxidoreductase of the mitochondrial disulfide relay Mia40. We identify cysteines at positions 27 and 64 in domain I of Ccs1 as critical for mitochondrial import and interaction with Mia40. On interaction with Mia40, these cysteines form a structural disulfide bond that stabilizes the overall fold of domain I. Although the cysteines are essential for the accumulation of functional Ccs1 in mitochondria, they are dispensable for the enzymatic activity of cytosolic Ccs1. We propose a model in which the Mia40-mediated oxidative folding of domain I controls the cellular distribution of Ccs1 and, consequently, active Sod1. The American Society for Cell Biology 2011-10-15 /pmc/articles/PMC3192855/ /pubmed/21865594 http://dx.doi.org/10.1091/mbc.E11-04-0293 Text en © 2011 Klöppel et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Klöppel, Christine
Suzuki, Yutaka
Kojer, Kerstin
Petrungaro, Carmelina
Longen, Sebastian
Fiedler, Sebastian
Keller, Sandro
Riemer, Jan
Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol
title Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol
title_full Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol
title_fullStr Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol
title_full_unstemmed Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol
title_short Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol
title_sort mia40-dependent oxidation of cysteines in domain i of ccs1 controls its distribution between mitochondria and the cytosol
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192855/
https://www.ncbi.nlm.nih.gov/pubmed/21865594
http://dx.doi.org/10.1091/mbc.E11-04-0293
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