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 journalArticlepeer-review

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

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