Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation.

The mitochondrial A3243G tRNALeu(UUR) mutation associated with a variety of mitochondrial disorders results in a severe respiratory deficiency, an increase in reactive oxygen species (ROS) production and activities of anti-oxidative enzyme in vitro. However, the phenotypic implications of this mutation have not been described in vivo. Here, mitochondria carrying A3243G transition from the peripheral blood of diabetes mellitus patients were microinjected into zygotes. Influence of this mutation on mitochondrial respiratory enzyme activities, ROS generation, and anti-oxidative enzyme activities in the heteroplasmic tissues of transmitochondrial mice was evaluated. The chimeric mice exhibited a subtle impaired oxidative phosphorylation, reduced activity of complex I/IV, increased activity of superoxide dismutase, and in turn, enhanced ROS generation. Our results suggest that mitochondrial A3243G mutation may be responsible for the high ROS production in vivo. Increased generation of ROS caused by mtDNA mutation may also play a role in the pathogenesis of the A3243G mutation-associated diseases.