Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782213809218256896 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3192855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kloppelchristine mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT suzukiyutaka mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT kojerkerstin mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT petrungarocarmelina mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT longensebastian mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT fiedlersebastian mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT kellersandro mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol AT riemerjan mia40dependentoxidationofcysteinesindomainiofccs1controlsitsdistributionbetweenmitochondriaandthecytosol |