Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
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
_version_ 1783333099327717376
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
work_keys_str_mv AT erdoganalicanj themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT alimuna themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT habichmarkus themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT salscheidersiljal themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT schulaura themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT petrungarocarmelina themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT thomaslukew themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT ashcroftmargaret themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT leichertlarsi themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT romaleticiaprates themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT riemerjan themitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT erdoganalicanj mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT alimuna mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT habichmarkus mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT salscheidersiljal mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT schulaura mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT petrungarocarmelina mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT thomaslukew mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT ashcroftmargaret mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT leichertlarsi mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT romaleticiaprates mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo
AT riemerjan mitochondrialoxidoreductasechchd4ispresentinasemioxidizedstateinvivo