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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 724018.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells
Authors:Al-Furoukh, N.; Ianni, A.; Nolte, H.; Holper, S.; Kruger, M.; Wanrooij, S.; Braun, T.
Date of Publication (YYYY-MM-DD):2015-10
Title of Journal:Biochim Biophys Acta
Volume:1853
Issue / Number:10 Pt A
Start Page:2580
End Page:2591
Audience:Not Specified
Abstract / Description: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 mitochondrial 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.
Free Keywords:Animals; Endopeptidase Clp/*biosynthesis/genetics; HEK293 Cells; Humans; Mice; Mitochondria/*enzymology/genetics; Mitochondrial Proteins/*biosynthesis/genetics; Multienzyme Complexes/genetics/metabolism; Transcription Factor CHOP/genetics/metabolism; Unfolded Protein Response/*physiology; CHOP/Ddit3/CEBPZ/GADD153; ClpXP; Myogenesis; Proteomics; Silac; UPR(mt) (mitochondrial unfolded protein response)
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, D-61231 Bad Nauheim, Germany. Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, D-50931 Cologne, Germany. Department of Medical Biochemistry and Biophysics, KBC, Kemihuset, University of Umea, SE-90187 Umea, Sweden.
Identifiers:ISSN:0006-3002 (Print) 0006-3002 (Linking) %R 10.1016/j.bbamcr.2015.06.016
URL:http://www.ncbi.nlm.nih.gov/pubmed/26142927
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