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The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo
Disulfide formation in the mitochondrial intermembrane space is an essential process catalyzed by a disulfide relay machinery. In mammalian cells, the key enzyme in this machinery is the oxidoreductase CHCHD4/Mia40. Here, we determined the in vivo CHCHD4 redox state, which is the major determinant o...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007816/ https://www.ncbi.nlm.nih.gov/pubmed/29704824 http://dx.doi.org/10.1016/j.redox.2018.03.014 |
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author | Erdogan, Alican J. Ali, Muna Habich, Markus Salscheider, Silja L. Schu, Laura Petrungaro, Carmelina Thomas, Luke W. Ashcroft, Margaret Leichert, Lars I. Roma, Leticia Prates Riemer, Jan |
author_facet | Erdogan, Alican J. Ali, Muna Habich, Markus Salscheider, Silja L. Schu, Laura Petrungaro, Carmelina Thomas, Luke W. Ashcroft, Margaret Leichert, Lars I. Roma, Leticia Prates Riemer, Jan |
author_sort | Erdogan, Alican J. |
collection | PubMed |
description | Disulfide formation in the mitochondrial intermembrane space is an essential process catalyzed by a disulfide relay machinery. In mammalian cells, the key enzyme in this machinery is the oxidoreductase CHCHD4/Mia40. Here, we determined the in vivo CHCHD4 redox state, which is the major determinant of its cellular activity. We found that under basal conditions, endogenous CHCHD4 redox state in cultured cells and mouse tissues was predominantly oxidized, however, degrees of oxidation in different tissues varied from 70% to 90% oxidized. To test whether differences in the ratio between CHCHD4 and ALR might explain tissue-specific differences in the CHCHD4 redox state, we determined the molar ratio of both proteins in different mouse tissues. Surprisingly, ALR is superstoichiometric over CHCHD4 in most tissues. However, the levels of CHCHD4 and the ratio of ALR over CHCHD4 appear to correlate only weakly with the redox state, and although ALR is present in superstoichiometric amounts, it does not lead to fully oxidized CHCHD4. |
format | Online Article Text |
id | pubmed-6007816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-60078162018-06-20 The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo Erdogan, Alican J. Ali, Muna Habich, Markus Salscheider, Silja L. Schu, Laura Petrungaro, Carmelina Thomas, Luke W. Ashcroft, Margaret Leichert, Lars I. Roma, Leticia Prates Riemer, Jan Redox Biol Short Communication Disulfide formation in the mitochondrial intermembrane space is an essential process catalyzed by a disulfide relay machinery. In mammalian cells, the key enzyme in this machinery is the oxidoreductase CHCHD4/Mia40. Here, we determined the in vivo CHCHD4 redox state, which is the major determinant of its cellular activity. We found that under basal conditions, endogenous CHCHD4 redox state in cultured cells and mouse tissues was predominantly oxidized, however, degrees of oxidation in different tissues varied from 70% to 90% oxidized. To test whether differences in the ratio between CHCHD4 and ALR might explain tissue-specific differences in the CHCHD4 redox state, we determined the molar ratio of both proteins in different mouse tissues. Surprisingly, ALR is superstoichiometric over CHCHD4 in most tissues. However, the levels of CHCHD4 and the ratio of ALR over CHCHD4 appear to correlate only weakly with the redox state, and although ALR is present in superstoichiometric amounts, it does not lead to fully oxidized CHCHD4. Elsevier 2018-03-24 /pmc/articles/PMC6007816/ /pubmed/29704824 http://dx.doi.org/10.1016/j.redox.2018.03.014 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Short Communication Erdogan, Alican J. Ali, Muna Habich, Markus Salscheider, Silja L. Schu, Laura Petrungaro, Carmelina Thomas, Luke W. Ashcroft, Margaret Leichert, Lars I. Roma, Leticia Prates Riemer, Jan The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo |
title | The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo |
title_full | The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo |
title_fullStr | The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo |
title_full_unstemmed | The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo |
title_short | The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo |
title_sort | mitochondrial oxidoreductase chchd4 is present in a semi-oxidized state in vivo |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007816/ https://www.ncbi.nlm.nih.gov/pubmed/29704824 http://dx.doi.org/10.1016/j.redox.2018.03.014 |
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