Lin Jason L J, Nakagawa Akihisa, Skeen-Gaar Riley, Yang Wei-Zen, Zhao Pei, Zhang Zhe, Ge Xiao, Mitani Shohei, Xue Ding, Yuan Hanna S
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 11529, ROC.
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Cell Rep. 2016 Jul 12;16(2):279-287. doi: 10.1016/j.celrep.2016.05.090. Epub 2016 Jun 23.
Endonuclease G (EndoG) is a mitochondrial protein that is released from mitochondria and relocated into the nucleus to promote chromosomal DNA fragmentation during apoptosis. Here, we show that oxidative stress causes cell-death defects in C. elegans through an EndoG-mediated cell-death pathway. In response to high reactive oxygen species (ROS) levels, homodimeric CPS-6-the C. elegans homolog of EndoG-is dissociated into monomers with diminished nuclease activity. Conversely, the nuclease activity of CPS-6 is enhanced, and its dimeric structure is stabilized by its interaction with the worm AIF homolog, WAH-1, which shifts to disulfide cross-linked dimers under high ROS levels. CPS-6 thus acts as a ROS sensor to regulate the life and death of cells. Modulation of the EndoG dimer conformation could present an avenue for prevention and treatment of diseases resulting from oxidative stress.
核酸内切酶G（EndoG）是一种线粒体蛋白，在细胞凋亡过程中从线粒体释放出来并重新定位到细胞核中，以促进染色体DNA片段化。在此，我们表明氧化应激通过EndoG介导的细胞死亡途径导致秀丽隐杆线虫出现细胞死亡缺陷。响应于高活性氧（ROS）水平，同型二聚体CPS-6（EndoG的秀丽隐杆线虫同源物）解离成核酸酶活性降低的单体。相反，CPS-6的核酸酶活性增强，并且其与线虫AIF同源物WAH-1的相互作用使其二聚体结构稳定，WAH-1在高ROS水平下转变为二硫键交联的二聚体。因此，CPS-6作为ROS传感器来调节细胞的生死。EndoG二聚体构象的调节可能为预防和治疗由氧化应激引起的疾病提供一条途径。
