title: Mitochondria Retrograde Signaling and the UPR mt: Where Are We in Mammals?
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 (UPR(mt)) 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 UPR(mt) could thus be initiated to boost folding and degradation capacity in response to unfolded and aggregated protein accumulation. Although first described in mammals, the UPR(mt) was mainly studied in Caenorhabditis elegans, and accumulating evidence suggests that mechanisms triggered in response to a UPR(mt) might be different in C. elegans and mammals. In this review, we discuss and integrate recent data from the literature to address whether the UPR(mt) 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.
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium. thierry.arnould@unamur.be.
authors.forename: Thierry
authors.initials: T
authors.lastname: Arnould
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium. sebastien.michel@unamur.be.|Department of Physiology, University of Lausanne, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland. sebastien.michel@unamur.be.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Michel
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium. patsy.renard@unamur.be.
authors.forename: Patricia
authors.initials: P
authors.lastname: Renard
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D056811:Unfolded Protein Response
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins
keywords: cell signaling; gene expression; mitochondria; unfolded protein response