Li J, Zhou K, Meng X, Wu Q, Li S, Liu Y, Wang J
Department of Laboratory Animal Science, Capital Medical University, Beijing, China.
Genet Mol Res. 2008 Oct 14;7(4):1054-62. doi: 10.4238/vol7-4gmr480.
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.
与多种线粒体疾病相关的线粒体A3243G tRNALeu（UUR）突变会导致严重的呼吸功能缺陷、活性氧（ROS）生成增加以及体外抗氧化酶活性增强。然而，该突变在体内的表型影响尚未见报道。在此，将携带A3243G突变的线粒体从糖尿病患者外周血中显微注射到受精卵中。评估了该突变对转线粒体小鼠异质组织中线粒体呼吸酶活性、ROS生成以及抗氧化酶活性的影响。嵌合小鼠表现出轻微的氧化磷酸化受损、复合体I/IV活性降低、超氧化物歧化酶活性增加，进而ROS生成增强。我们的结果表明，线粒体A3243G突变可能是体内ROS高生成的原因。由线粒体DNA突变引起的ROS生成增加也可能在A3243G突变相关疾病的发病机制中起作用。
