Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria.
Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria.
复制标题
DOI：
10.3164/jcbn.14-134
复制
发表时间：
2015-03
影响因子：
2.4
通讯作者：
Ozaki T
中科院分区：
文献类型：
--
作者：
Itoh K;Ye P;Matsumiya T;Tanji K;Ozaki T
核因子红细胞衍生2相关因子2（Nrf 2）最初被确定为药物解毒酶基因表达的正调控因子，在暴露于环境亲电体。目前，已知Nrf 2调节数百种细胞保护基因的表达，以抵消内源性或外源性产生的氧化应激。此外，当在人类肿瘤中通过体细胞突变激活时，Nrf 2通过调节参与各种过程的基因（如磷酸戊糖途径和核苷酸合成以及抗氧化蛋白）来赋予生长优势和化学抗性。有趣的是，越来越多的证据表明，Nrf 2与某些组织（如心脏）在环境应激期间的线粒体生物合成有关。此外，还对C.秀丽线虫，被线粒体活性氧物质激活并通过促进线粒体体内平衡延长寿命（即，mitochormesis）。类似地，最近在过量位点蛋白1（Surf 1）-/-小鼠的心脏中观察到Nrf 2激活，其中细胞呼吸由于细胞色素c氧化酶缺陷而降低。在这篇综述中，我们批判性地研究了Nrf 2和线粒体之间的关系，并认为Nrf 2应激途径与线粒体密切沟通，以维持细胞在氧化应激过程中的稳态。
Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) was originally identified as a positive regulator of drug detoxifying enzyme gene expression during exposure to environmental electrophiles. Currently, Nrf2 is known to regulate the expression of hundreds of cytoprotective genes to counteract endogenously or exogenously generated oxidative stress. Furthermore, when activated in human tumors by somatic mutations, Nrf2 confers growth advantages and chemoresistance by regulating genes involved in various processes such as the pentose phosphate pathway and nucleotide synthesis in addition to antioxidant proteins. Interestingly, increasing evidence shows that Nrf2 is associated with mitochondrial biogenesis during environmental stresses in certain tissues such as the heart. Furthermore, SKN-1, a functional homolog of Nrf2 in C. elegans, is activated by mitochondrial reactive oxygen species and extends life span by promoting mitochondrial homeostasis (i.e., mitohormesis). Similarly, Nrf2 activation was recently observed in the heart of surfeit locus protein 1 (Surf1) -/- mice in which cellular respiration was decreased due to cytochrome c oxidase defects. In this review, we critically examine the relationship between Nrf2 and mitochondria and argue that the Nrf2 stress pathway intimately communicates with mitochondria to maintain cellular homeostasis during oxidative stress.
登录
查看更多内容
影响因子：
4.3
作者：
Abrahamsen G;Fan Y;Matigian N;Wali G;Bellette B;Sutharsan R;Raju J;Wood SA;Veivers D;Sue CM;Mackay-Sim A
通讯作者：
Mackay-Sim A
影响因子：
3.3
作者：
Barhwal, K.;Hota, S. K.;Ilavazhagan, G.
通讯作者：
Ilavazhagan, G.
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
4.4
作者：
Indo, Hiroko P.;Davidson, Mercy;Majima, Hideyuki J.
通讯作者：
Majima, Hideyuki J.