Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control.
Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control.
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DOI：
10.1016/j.molcel.2012.07.002
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发表时间：
2012-09-28
期刊：
影响因子：
16
通讯作者：
Zhou Songyang
中科院分区：
文献类型：
--
作者：
Chen, Liuh-Yow;Zhang, Yi;Zhang, Qinfen;Li, Hongzhi;Luo, Zhenhua;Fang, Hezhi;Kim, Sok Ho;Qin, Li;Yotnda, Patricia;Xu, Jianming;Tu, Benjamin P.;Bai, Yidong;Zhou Songyang
线粒体是代谢动力，端粒有助于维持基因组的稳定性，两者都与癌症和衰老有关。然而，连接这两种细胞结构的信号事件仍然知之甚少。在这里，我们报告说，典型的端粒蛋白TIN 2也是一个调节代谢。TIN 2被募集到端粒并与包括TPP 1在内的多个端粒调节因子相关联。TPP 1与含有重叠的线粒体和端粒靶向序列的TIN 2 N-末端相互作用，并控制TIN 2定位。我们发现TIN 2在线粒体中进行后加工，并调节线粒体氧化磷酸化。通过RNAi敲低降低TIN 2表达抑制了糖酵解和活性氧（ROS）的产生，并提高了癌细胞中的ATP水平和氧消耗。这些结果表明端粒蛋白和代谢控制之间的联系，提供了一个额外的机制，端粒蛋白调节癌症和衰老。
Both mitochondria, which are metabolic powerhouses, and telomeres, which help maintain genomic stability, have been implicated in cancer and aging. However, the signaling events that connect these two cellular structures remain poorly understood. Here we report that the canonical telomeric protein TIN2 is also a regulator of metabolism. TIN2 is recruited to telomeres and associates with multiple telomere regulators including TPP1. TPP1 interacts with TIN2 N-terminus, which contains overlapping mitochondrial and telomeric targeting sequences, and controls TIN2 localization. We have found that TIN2 is post-translationally processed in mitochondria, and regulates mitochondria oxidative phosphorylation. Reducing TIN2 expression by RNAi knockdown inhibited glycolysis and reactive oxygen species (ROS) and production, and enhanced ATP levels and oxygen consumption in cancer cells. These results suggest a link between telomeric proteins and metabolic control, providing an additional mechanism by which telomeric proteins regulate cancer and aging.
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