Sirt3, mitochondrial ROS, ageing, and carcinogenesis.
Sirt3, mitochondrial ROS, ageing, and carcinogenesis.
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DOI：
10.3390/ijms12096226
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发表时间：
2011
影响因子：
5.6
通讯作者：
Kim HS
中科院分区：
文献类型：
--
作者：
Park SH;Ozden O;Jiang H;Cha YI;Pennington JD;Aykin-Burns N;Spitz DR;Gius D;Kim HS
癌症病因学中的一个基本观察结果是，任何哺乳动物群体中的恶性肿瘤发生率均随年龄呈指数增加，这表明控制寿命和致癌作用的细胞过程之间存在机械联系。此外，众所周知，在衰老和癌症中均观察到线粒体代谢的畸变，如通过增加的活性氧（ROS）所测量的。在这方面，影响长寿的基因最近已经在S。cerevisiae和C.线虫，并且人类同源物包括蛋白脱乙酰酶的Sirtuin家族。有趣的是，七种sirtuin蛋白中的三种定位于线粒体中，这表明线粒体sirtuins、衰老的自由基理论和致癌作用之间存在联系。基于这些结果，已经假设Sirt 3作为线粒体保真度蛋白发挥功能，其功能通过调节ROS代谢来控制衰老和癌变。Sirt 3现在也已被确定为基因组表达，线粒体定位的肿瘤抑制因子，这篇综述将概述线粒体ROS/超氧化物水平，衰老和细胞表型允许雌激素和孕激素受体阳性乳腺癌发生之间的潜在关系。
One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS), are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans, and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor and this review will outline potential relationships between mitochondrial ROS/superoxide levels, aging, and cell phenotypes permissive for estrogen and progesterone receptor positive breast carcinogenesis.
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