Universität zu Köln

Habich, Markus, Salscheider, Silja Lucia, Murschall, Lena Maria, Hoehne, Michaela Nicole, Fischer, Manuel, Schorn, Fabian, Petrungaro, Carmelina, Ali, Muna, Erdogan, Alican J., Abou-Eid, Shadi, Kashkar, Hamid, Dengjel, Joern ORCID: 0000-0002-9453-4614 and Riemer, Jan (2019). Vectorial Import via a Metastable Disulfide-Linked Complex Allows for a Quality Control Step and Import by the Mitochondrial Disulfide Relay. Cell Reports, 26 (3). S. 759 - 780. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Disulfide formation in the mitochondrial intermembrane space (IMS) is an essential process. It is catalyzed by the disulfide relay machinery, which couples substrate import and oxidation. The machinery relies on the oxidoreductase and chaperone CHCHD4-Mia40. Here, we report on the driving force for IMS import and on a redox quality control mechanism. We demonstrate that unfolded reduced proteins, upon translocation into the IMS, initiate formation of a metastable disulfide-linked complex with CHCHD4. If this interaction does not result in productive oxidation, then substrates are released to the cytosol and degraded by the proteasome. Based on these data, we propose a redox quality control step at the level of the disulfide-linked intermediate that relies on the vectorial nature of IMS import. Our findings also provide the mechanistic framework to explain failures in import of numerous human disease mutants in CHCHD4 substrates.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Habich, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Salscheider, Silja Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Murschall, Lena Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoehne, Michaela Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Schorn, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Petrungaro, Carmelina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ali, Muna UNSPECIFIED UNSPECIFIED UNSPECIFIED Erdogan, Alican J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abou-Eid, Shadi UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED Dengjel, Joern UNSPECIFIED orcid.org/0000-0002-9453-4614 UNSPECIFIED Riemer, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-159239
DOI:	10.1016/j.celrep.2018.12.092
Journal or Publication Title:	Cell Reports
Volume:	26
Number:	3
Page Range:	S. 759 - 780
Date:	2019
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERMEMBRANE SPACE; ELECTRON-TRANSFER; STRUCTURAL BASIS; PROTEIN IMPORT; BOND FORMATION; MIA40; BIOGENESIS; SYSTEM; IDENTIFICATION; OXIDOREDUCTASE Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15923