A Novel Protective Role for p130 in Neuron Oxidative Stress

The human brain is the most energy-consuming and highly oxidative organ in the body. It generates high levels of mitochondrial reactive oxygen species (ROS), damaging proteins and DNA. This is evident in neurodegenerative diseases and aging where the brains defence mechanisms prove insufficient. We provide insight into a novel mechanism of ROS defence in the brain, mediated via p130 that limits oxidative phosphorylation. Conditions of increased metabolic stress or treatment of neurons with ROS inducing agent resulted in mitochondrial localization of p130 in neurons. In the mitochondria, p130 bound to mitochondrial DNA and was associated with decreased mitochondrial gene expression. This resulted in decreased ATP production, thus limiting ROS generation. Our results highlight a new understanding of transcriptional regulation of the mitochondrial genome by the nuclear transcriptional corepressor p130. This might serve as a potential mechanism to control ROS production of neurons in response to increased metabolic stress.