Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat.

Gloria E Villalpando-Rodriguez,Spencer B Gibson,Jesús Tejero

doi:10.1155/2021/9912436

Gloria E Villalpando-Rodriguez, Spencer B Gibson + Show 1 more

Open Access

https://doi.org/10.1155/2021/9912436

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Abstract

Reactive oxygen species (ROS) are essential for cellular signaling and response to stress. The level of ROS and the type of ROS determine the ability of cells to undergo cell death. Furthermore, dysregulation of the antioxidant pathways is associated with many diseases. It has become apparent that cell death can occur through different mechanisms leading to the classifications of different types of cell death such as apoptosis, ferroptosis, and necroptosis. ROS play essential roles in all forms of cell death, but it is only now coming into focus that ROS control and determine the type of cell death that occurs in any given cell. Indeed, ROS may act as a rheostat allowing different cell death mechanisms to be engaged and crosstalk with different cell death types. In this review, we will describe the ROS regulatory pathways and how they control different types of cell death under normal and disease states. We will also propose how ROS could provide a mechanism of crosstalk between cell death mechanisms and act as a rheostat determining the type of cell death.

Highlights

Cellular reactive oxygen species (ROS) are tightly controlled to dictate different cell fates, such as differentiation or cell survival
MiaPaCa-2 cells do not express RIP3, only RIP1. These results suggested that TNF-related apoptosis-inducing ligand (TRAIL) treatment of MiaPaCa-2 and BxPC-3 cells under inhibition of peroxide promotes RIP1dependent necroptosis, and that TRAIL treatment under inhibition of ROS promotes RIP3-dependent necroptosis in BxPC-3 cells [119]
Mlkl-knockout cells were protected against necroptosis induced by the combination but died by ferroptosis when treated with erastin and RSL3

Summary

Introduction

Cellular reactive oxygen species (ROS) are tightly controlled to dictate different cell fates, such as differentiation or cell survival. When ROS are produced in excess, such as in cells under metabolic stress, this leads to cell death This suggests that a “ROS rheostat” exists in cells controlling cellular survival. Other forms of cell death were described under different physiological conditions such as iron-mediated cell death, ferroptosis, and autophagy- (selfeating-) induced cell death. ROS produced by cells under stress, or cells with reduced antioxidant capacity, can determine whether the cell survives or dies, Oxidative Medicine and Cellular Longevity and the type of cell death mechanism engaged This ability of ROS to act as a rheostat determining cell death but the type of cell death is only coming into focus under pathological or physiological conditions. This review will explore the importance of ROS and its signalling on different types of cell death and how ROS acts a rheostat to determine different types of cell death

Regulation of ROS Production and Antioxidants

ROS Signaling

ROS in Different Types of Cell Death

ROS and Cell Death in Disease

Perspective and Future Questions

Conclusion