Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages

ED Yoboue, R Sitia, T Simmen

Research output: Contribution to journalArticle

Abstract

Many cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (H 2 O 2 ) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a "redox triangle" formed by mitochondria, peroxisomes and the ER, assembling "redoxosomes" that sense ROS accumulations and redox imbalances. The redoxosome enzymes use ROS, potentially toxic by-products made by some redoxosome members themselves, to transmit inter-compartmental signals via chemical modifications of downstream proteins and lipids. Interestingly, important components of the redoxosome are ER chaperones and oxidoreductases, identifying ER oxidative protein folding as a key ROS producer and controller of the tri-organellar membrane contact sites (MCS) formed at the redox triangle. At these MCS, ROS accumulations could directly facilitate inter-organellar signal transmission, using ROS transporters. In addition, ROS influence the flux of Ca 2+ ions, since many Ca 2+ handling proteins, including inositol 1,4,5 trisphosphate receptors (IP 3 Rs), SERCA pumps or regulators of the mitochondrial Ca 2+ uniporter (MCU) are redox-sensitive. Fine-tuning of these redox and ion signaling pathways might be difficult in older organisms, suggesting a dysfunctional redox triangle may accompany the aging process. © 2018 The Author(s).
Original languageEnglish
Article number331
JournalCell Death and Disease
Volume9
Issue number3
DOIs
Publication statusPublished - 2018

Fingerprint

Poisons
Endoplasmic Reticulum
Oxidation-Reduction
Reactive Oxygen Species
Membranes
Peroxisomes
Mitochondria
Ions
Inositol 1,4,5-Trisphosphate Receptors
Protein Folding
Enzymes
Organelles
Hydrogen Peroxide
Oxidoreductases
Proteins
Lipids

Cite this

Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages. / Yoboue, ED; Sitia, R; Simmen, T.

In: Cell Death and Disease, Vol. 9, No. 3, 331, 2018.

Research output: Contribution to journalArticle

@article{eb383f361d624aeca79a3953e97f8cd3,
title = "Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages",
abstract = "Many cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (H 2 O 2 ) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a {"}redox triangle{"} formed by mitochondria, peroxisomes and the ER, assembling {"}redoxosomes{"} that sense ROS accumulations and redox imbalances. The redoxosome enzymes use ROS, potentially toxic by-products made by some redoxosome members themselves, to transmit inter-compartmental signals via chemical modifications of downstream proteins and lipids. Interestingly, important components of the redoxosome are ER chaperones and oxidoreductases, identifying ER oxidative protein folding as a key ROS producer and controller of the tri-organellar membrane contact sites (MCS) formed at the redox triangle. At these MCS, ROS accumulations could directly facilitate inter-organellar signal transmission, using ROS transporters. In addition, ROS influence the flux of Ca 2+ ions, since many Ca 2+ handling proteins, including inositol 1,4,5 trisphosphate receptors (IP 3 Rs), SERCA pumps or regulators of the mitochondrial Ca 2+ uniporter (MCU) are redox-sensitive. Fine-tuning of these redox and ion signaling pathways might be difficult in older organisms, suggesting a dysfunctional redox triangle may accompany the aging process. {\circledC} 2018 The Author(s).",
author = "ED Yoboue and R Sitia and T Simmen",
year = "2018",
doi = "10.1038/s41419-017-0033-4",
language = "English",
volume = "9",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages

AU - Yoboue, ED

AU - Sitia, R

AU - Simmen, T

PY - 2018

Y1 - 2018

N2 - Many cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (H 2 O 2 ) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a "redox triangle" formed by mitochondria, peroxisomes and the ER, assembling "redoxosomes" that sense ROS accumulations and redox imbalances. The redoxosome enzymes use ROS, potentially toxic by-products made by some redoxosome members themselves, to transmit inter-compartmental signals via chemical modifications of downstream proteins and lipids. Interestingly, important components of the redoxosome are ER chaperones and oxidoreductases, identifying ER oxidative protein folding as a key ROS producer and controller of the tri-organellar membrane contact sites (MCS) formed at the redox triangle. At these MCS, ROS accumulations could directly facilitate inter-organellar signal transmission, using ROS transporters. In addition, ROS influence the flux of Ca 2+ ions, since many Ca 2+ handling proteins, including inositol 1,4,5 trisphosphate receptors (IP 3 Rs), SERCA pumps or regulators of the mitochondrial Ca 2+ uniporter (MCU) are redox-sensitive. Fine-tuning of these redox and ion signaling pathways might be difficult in older organisms, suggesting a dysfunctional redox triangle may accompany the aging process. © 2018 The Author(s).

AB - Many cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (H 2 O 2 ) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a "redox triangle" formed by mitochondria, peroxisomes and the ER, assembling "redoxosomes" that sense ROS accumulations and redox imbalances. The redoxosome enzymes use ROS, potentially toxic by-products made by some redoxosome members themselves, to transmit inter-compartmental signals via chemical modifications of downstream proteins and lipids. Interestingly, important components of the redoxosome are ER chaperones and oxidoreductases, identifying ER oxidative protein folding as a key ROS producer and controller of the tri-organellar membrane contact sites (MCS) formed at the redox triangle. At these MCS, ROS accumulations could directly facilitate inter-organellar signal transmission, using ROS transporters. In addition, ROS influence the flux of Ca 2+ ions, since many Ca 2+ handling proteins, including inositol 1,4,5 trisphosphate receptors (IP 3 Rs), SERCA pumps or regulators of the mitochondrial Ca 2+ uniporter (MCU) are redox-sensitive. Fine-tuning of these redox and ion signaling pathways might be difficult in older organisms, suggesting a dysfunctional redox triangle may accompany the aging process. © 2018 The Author(s).

U2 - 10.1038/s41419-017-0033-4

DO - 10.1038/s41419-017-0033-4

M3 - Article

VL - 9

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 3

M1 - 331

ER -