Cellular targets of oxidative stress

Abstract

There are three major sites of oxidant production in the cell; mitochondria, endoplasmic reticulum (ER), and peroxisomes. Each is equipped with their own antioxidant system to prevent injury and protect subcellular functions. Mitochondria are essential to produce energy through respiratory chain activity and injury involves disruption of respiratory complexes and accelerated production and release of O2ˉ˙. ER is essential for protein processing and Ca²⁺ homeostasis, and interruption of ER functions results in upregulation of the unfolded protein response and initiation of ER stress. Uncontrolled ER stress results in aberrant Ca²⁺ regulation, production and release of reactive oxygen species, and activation of autophagy and apoptosis pathways. Peroxisomal function is tightly correlated to both mitochondria and ER and disruption precipitates release of H₂O₂ into the cellular milieu. Drugs, environmental toxins, and aging all contribute to organelle injury and release of ROS, resulting in cardiovascular and neurological diseases and cancers.