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

Research output: Contribution to journalLiterature review

120 Downloads (Pure)

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

Fingerprint

mammals
Mitochondria
Mammals
mitochondria
Mitochondrial Proteins
Unfolded Protein Response
Protein Unfolding
Proteins
proteins
Proteome
Mitochondrial DNA
Quality Control
Organelles
Homeostasis
folding
proteome
Quality control
homeostasis
organelles
Chemical activation

Keywords

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

Cite this

@article{845b82b5ea0a4e78b6dd5cda76bee017,
title = "Mitochondria retrograde signaling and the UPRmt: 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 (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.",
keywords = "Cell signaling, Gene expression, Mitochondria, Unfolded protein response",
author = "Thierry Arnould and S{\'e}bastien Michel and Patricia Renard",
year = "2015",
doi = "10.3390/ijms160818224",
language = "English",
volume = "16",
pages = "18224--18251",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

TY - JOUR

T1 - Mitochondria retrograde signaling and the UPRmt: Where are we in mammals?

AU - Arnould, Thierry

AU - Michel, Sébastien

AU - Renard, Patricia

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Cell signaling

KW - Gene expression

KW - Mitochondria

KW - Unfolded protein response

UR - http://www.scopus.com/inward/record.url?scp=84938863498&partnerID=8YFLogxK

U2 - 10.3390/ijms160818224

DO - 10.3390/ijms160818224

M3 - Literature review

AN - SCOPUS:84938863498

VL - 16

SP - 18224

EP - 18251

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 8

ER -