Manganese superoxide dismutase versus p53: the mitochondrial center

Mitochondria are important sites of myriad metabolic activities. The actions of mitochondria must be carefully synchronized with other processes in the cell to maintain cellular homeostasis. Interorganellar communication between mitochondria and the nucleus is key for coordination of these cellular functions. Numerous signaling proteins and transcription factors are affected by reactive oxygen species and aid interorganellar communication. p53 is an important tumor suppressing protein that regulates many cellular activities, such as cell cycle regulation, DNA repair, and programmed cell death. p53 carries out these functions through both transcription-dependent and transcription-independent routes at mitochondria and the nucleus. Manganese superoxide dismutase (MnSOD), a p53-regulated gene that is a vital antioxidant enzyme localized in the matrix of mitochondria, scavenges reactive oxygen species. Recent studies suggest that mitochondria can regulate p53 activity and that assaults on the cell that affect mitochondrial ROS production and mitochondrial function can influence p53 activity. Cross-talk between mitochondria and p53 is important in normal cellular functions, and a breakdown in communication among mitochondria, p53, and the nucleus may have serious consequences in disease development.