Universität zu Köln

Al-Furoukh, Natalie, Ianni, Alessandro ORCID: 0000-0001-7398-589X, Nolte, Hendrik, Hoelper, Soraya, Krueger, Marcus ORCID: 0000-0003-2008-4582, Wanrooij, Sjoerd ORCID: 0000-0001-6126-4382 and Braun, Thomas ORCID: 0000-0002-6165-4804 (2015). ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells. Biochim. Biophys. Acta-Mol. Cell Res., 1853 (10). S. 2580 - 2592. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1879-2596

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Abstract

Proteostasis is crucial for life and maintained by cellular chaperones and proteases. One major mitochondrial protease is the ClpXP complex, which is comprised of a catalytic ClpX subunit and a proteolytic ClpP subunit. Based on two separate observations, we hypothesized that ClpX may play a leading role in the cellular function of ClpXP. Therefore, we analyzed the effect of ClpX overexpression on a myoblast proteome by quantitative proteomics. ClpX overexpression results in the upregulation of markers of the mitochondria( proteostasis pathway, known as the mitochondrial unfolded protein response (UPRmt). Although this pathway is described in detail in Caenorhabditis elegans, it is not clear whether it is conserved in mammals. Therefore, we compared features of the classical nematode UPRmt with our mammalian ClpX-triggered UPRmt dataset. We show that they share the same retrograde mitochondria-to-nucleus signaling pathway that involves the key UPRmt transcription factor CHOP (also known as Ddit3, CEBPZ or GADD153). In conclusion, our data confirm the existence of a mammalian UPRmt that has great similarity to the C elegans pathway. Furthermore, our results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells. (C) 2015 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Al-Furoukh, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Ianni, Alessandro UNSPECIFIED orcid.org/0000-0001-7398-589X UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelper, Soraya UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Wanrooij, Sjoerd UNSPECIFIED orcid.org/0000-0001-6126-4382 UNSPECIFIED Braun, Thomas UNSPECIFIED orcid.org/0000-0002-6165-4804 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-391874
DOI:	10.1016/j.bbamcr.2015.06.016
Journal or Publication Title:	Biochim. Biophys. Acta-Mol. Cell Res.
Volume:	1853
Number:	10
Page Range:	S. 2580 - 2592
Date:	2015
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1879-2596
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSCRIPTION FACTOR; LON PROTEASE; LONGEVITY; DEGRADATION; BIOGENESIS; EXPRESSION; DISCOVERY; STRESS; ACCUMULATION; RECOGNITION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/39187