Sato Nobuhiro
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S1-6. doi: 10.1111/j.1440-1746.2007.04963.x.
Mitochondria play a central role in cellular energy metabolism. Oxidative phosphorylation occurs in the electron transport system of the inner mitochondrial membrane. Cytochrome aa3, b and c1 are encoded by mitochondrial DNA whereas cytochrome c is encoded by the nuclear gene, and these mitochondrial-DNA dependent cytochromes are decreased and electron transport at complex II, III and IV is disturbed in liver carcinomas and during carcinogenesis. The more the decreased cytochrome and oxidase activity are seen, the more significant is the increase in reactive oxygen species (ROS) production. ROS produced in mitochondria may be the main cause of nuclear-gene mutation in carcinogenesis. The mitochondrial dysfunction and overproduction of ROS plays a key role in progression of chronic hepatitis C and ethanol-induced liver injury. Ethanol also causes bacterial translocation in the intestine and the resulting lipopolysaccharides (LPS) activates Kupffer cells to produce pro-inflammatory cytokines. We suspect that non-alcoholic steatohepatitis (NASH) also is the result of increased ROS production in Kupffer cells and hepatocytes.
线粒体在细胞能量代谢中起核心作用。氧化磷酸化发生在线粒体内膜的电子传递系统中。细胞色素aa3、b和c1由线粒体DNA编码，而细胞色素c由核基因编码，在肝癌及致癌过程中，这些依赖线粒体DNA的细胞色素减少，且复合物II、III和IV处的电子传递受到干扰。细胞色素和氧化酶活性降低越明显，活性氧（ROS）生成增加就越显著。线粒体中产生的ROS可能是致癌过程中核基因突变的主要原因。线粒体功能障碍和ROS过量产生在慢性丙型肝炎进展及乙醇诱导的肝损伤中起关键作用。乙醇还会导致肠道细菌移位，由此产生的脂多糖（LPS）激活库普弗细胞以产生促炎细胞因子。我们怀疑非酒精性脂肪性肝炎（NASH）也是库普弗细胞和肝细胞中ROS生成增加的结果。
