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ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2015 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1853, no 10, 2580-2591 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 1853, no 10, 2580-2591 p.
Keyword [en]
UPRmt (mitochondrial unfolded protein response), ClpXP, Proteomics, SILAC, Myogenesis, CHOP/Ddit3/CEBPZ/GADD153
National Category
Cell Biology Biochemistry and Molecular Biology
URN: urn:nbn:se:umu:diva-110504DOI: 10.1016/j.bbamcr.2015.06.016.ISI: 000361775100036PubMedID: 26142927OAI: diva2:894442
Available from: 2016-01-15 Created: 2015-10-22 Last updated: 2016-01-15Bibliographically approved

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Al-Furoukh, NatalieWanrooij, Sjoerd
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