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Int. J. Mol. Sci. 2015, 16(8), 18224-18251; doi:10.3390/ijms160818224

Mitochondria Retrograde Signaling and the UPRmt: Where Are We in Mammals?

1
Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium
2
Department of Physiology, University of Lausanne, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editors: Lars Olson, Jaime M. Ross and Giuseppe Coppotelli
Received: 24 May 2015 / Revised: 26 June 2015 / Accepted: 24 July 2015 / Published: 6 August 2015
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
View Full-Text   |   Download PDF [2630 KB, uploaded 6 August 2015]   |  

Abstract

Mitochondrial unfolded protein response is a form of retrograde signaling that contributes to ensuring the maintenance of quality control of mitochondria, allowing functional integrity of the mitochondrial proteome. When misfolded proteins or unassembled complexes accumulate beyond the folding capacity, it leads to alteration of proteostasis, damages, and organelle/cell dysfunction. Extensively studied for the ER, it was recently reported that this kind of signaling for mitochondrion would also be able to communicate with the nucleus in response to impaired proteostasis. The mitochondrial unfolded protein response (UPRmt) is activated in response to different types and levels of stress, especially in conditions where unfolded or misfolded mitochondrial proteins accumulate and aggregate. A specific UPRmt could thus be initiated to boost folding and degradation capacity in response to unfolded and aggregated protein accumulation. Although first described in mammals, the UPRmt was mainly studied in Caenorhabditis elegans, and accumulating evidence suggests that mechanisms triggered in response to a UPRmt might be different in C. elegans and mammals. In this review, we discuss and integrate recent data from the literature to address whether the UPRmt is relevant to mitochondrial homeostasis in mammals and to analyze the putative role of integrated stress response (ISR) activation in response to the inhibition of mtDNA expression and/or accumulation of mitochondrial mis/unfolded proteins. View Full-Text
Keywords: mitochondria; unfolded protein response; cell signaling; gene expression mitochondria; unfolded protein response; cell signaling; gene expression
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Arnould, T.; Michel, S.; Renard, P. Mitochondria Retrograde Signaling and the UPRmt: Where Are We in Mammals? Int. J. Mol. Sci. 2015, 16, 18224-18251.

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