Al-Furoukh, Natalie, Ianni, Alessandro ORCID: 0000-0001-7398-589X, Nolte, Hendrik, Hoelper, Soraya, Krueger, Marcus, 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:
CreatorsEmailORCIDORCID Put Code
Al-Furoukh, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ianni, AlessandroUNSPECIFIEDorcid.org/0000-0001-7398-589XUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelper, SorayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wanrooij, SjoerdUNSPECIFIEDorcid.org/0000-0001-6126-4382UNSPECIFIED
Braun, ThomasUNSPECIFIEDorcid.org/0000-0002-6165-4804UNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSCRIPTION FACTOR; LON PROTEASE; LONGEVITY; DEGRADATION; BIOGENESIS; EXPRESSION; DISCOVERY; STRESS; ACCUMULATION; RECOGNITIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39187

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