Mitochondria retrograde signaling and the UPRmt: Where are we in mammals?

Thierry Arnould, Sébastien Michel, Patricia Renard

Research output: Contribution to journalLiterature review

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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.
Original languageEnglish
Pages (from-to)18224-18251
Number of pages28
JournalInternational Journal of Molecular Sciences
Volume16
Issue number8
Early online date6 Aug 2015
DOIs
Publication statusPublished - 2015

Keywords

  • Cell signaling
  • Gene expression
  • Mitochondria
  • Unfolded protein response

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