Abstract
Rreactive oxygens (ROS) and nitric oxide (NO) are important for aerobic life and the etiology of various diseases. We hypothesized that overflow of free electrons from mitochondria is the critical cause for ROS generation. Kinetic analysis revealed that mitochondrial generation of ROS was enhanced either by respiratory substrates and Ca2+ or by electron transport inhibitors particularly under high energy status and that the generated ROS oxidized the critical SH of adenine nucleotide translocase to release ctochrome c, thereby stimulating the process of apoptosis. Targetting carnitine or SOD markedly inhibited the oxidation of the critical SH and the release of cytochrome c. Thus, ROS generated by perturbed mitochondria determins the fate of cells and tissues. ROS and/or NO impaires DNA in symbiotic bacteria and their hosts; the former enhances the mutation that accelerates their evolution while the latter enhances the process of aging and carcinogenesis. Based on such findings, critical roles of mitochondria and ROS/NO in the mechanism of evolution, life, aging and age-associated diseases will be discussed. [J Radiat Res 44:385 (2003)]
