Kim YongJoong, Kim Hag Dong, Kim Joon
Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Biochim Biophys Acta. 2013 Dec;1833(12):2943-2952. doi: 10.1016/j.bbamcr.2013.07.015. Epub 2013 Jul 30.
Ribosomal protein S3 (rpS3) is known to play critical roles in ribosome biogenesis and DNA repair. When cellular ROS levels increase, the mitochondrial genes are highly vulnerable to DNA damage. Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair while significantly decreasing the cellular protein synthesis. For the entrance into the mitochondria, the accumulation of rpS3 was regulated by interaction with HSP90, HSP70, and TOM70. Pretreatment with geldanamycin, which binds to the ATP pocket of HSP90, significantly decreased the interaction of rpS3 with HSP90 and stimulated the accumulation of rpS3 in the mitochondria. Furthermore, cellular ROS was decreased and mtDNA damage was rescued when levels of rpS3 were increased in the mitochondria. Therefore, we concluded that when mitochondrial DNA damages accumulate due to increased levels of ROS, rpS3 accumulates in the mitochondria to repair damaged DNA due to the decreased interaction between rpS3 and HSP90 in the cytosol.
已知核糖体蛋白S3（rpS3）在核糖体生物合成和DNA修复中发挥关键作用。当细胞内活性氧（ROS）水平升高时，线粒体基因极易受到DNA损伤。ROS增加会诱导rpS3在线粒体中积累以进行DNA修复，同时显著降低细胞蛋白质合成。对于进入线粒体而言，rpS3的积累受其与热休克蛋白90（HSP90）、热休克蛋白70（HSP70）和转位酶外膜70（TOM70）相互作用的调节。与HSP90的ATP口袋结合的格尔德霉素预处理显著降低了rpS3与HSP90的相互作用，并刺激了rpS3在线粒体中的积累。此外，当线粒体中rpS3水平升高时，细胞内ROS减少，线粒体DNA损伤得到修复。因此，我们得出结论，当由于ROS水平升高导致线粒体DNA损伤积累时，由于rpS3与胞质溶胶中HSP90之间的相互作用减少，rpS3在线粒体中积累以修复受损DNA。
