Mechanism of Generation of Reactive Oxygen Species from Mitochondria by Nuclear Signal

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Reactive oxygen species (ROS) seem to be an inducer of various diseases and pathogenesis such as aging, neuro-degenerative diseases, i.e., Alzheimer's disease, Parkinson's disease etc. Since we have reported the first evidence that mitochondrial generation of ROS controls apoptosis (Majima et al. JBC 1998), we have investigated the relationship between ROS and apoptosis, caused by radiation, blue light exposure, ischemia reperfusion, chemotherapeutic agent treatments (bleomycin and cis-platinum). In every experiments tested, we have confirmed the relationship among ROS, lipid peroxidation and apoptosis.In this study, we further investigated nuclear genome activation in mitochondrial DNA lacking cells (Rho0 cells) by DNA microarray, and found out that 402 genes out of 2236 nuclear genes were changed in Rho0 cells, suggesting a possible cross-talk messengers between mitochondria and nucleus. To test a possible role of p53 and hsp70 on the cross-talk messenger, we suppressed mRNA expression level by these RNAi, and studied change of ROS generation from mitochondria. A positive increase in ROS by transfection of MnSOD RNAi vectors was found, while no change of ROS by transfection of p53 or hsp70 RNAi vectors were revealed, suggesting p53 and HSP70 are not candidate of the cross-talk messenger.