7月20日,Cell Metab杂志在线报道,线粒体蛋白CRIF1通过与新生的氧化磷酸化多肽及分子伴侣相互作用调节线粒体编码的氧化磷酸化多肽的合成和插入线粒体内膜过程。
虽然对线粒体DNA编码多肽表达机制的研究已经取得了很大的进展,参与线粒体核蛋白体介导的多肽合成和将线粒体氧化磷酸化(OXPHOS)多肽自发插入线粒体内膜过程的调控因子目前还不清楚。
在本研究中,干扰编码线粒体蛋白的小鼠Crif1基因表达,可导致体内因氧化磷酸化亚基和复合物消失所造成的氧化磷酸化的严重缺陷。CRIF1与线粒体核蛋白体大亚基联系在一起,定位在靠近多肽输出隧道的出口处,消除CRIF1的表达导致线粒体DNA编码的氧化磷酸化新生多肽的异常合成和有缺陷地插入线粒体内层膜。CRIF1与新生的氧化磷酸化多肽及分子伴侣,例如,Tid1,相互作用。
这些结果表明,CRIF1在哺乳动物氧化磷酸化多肽整合入线粒体膜的过程中发挥关键作用。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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CRIF1 Is Essential for the Synthesis and Insertion of Oxidative Phosphorylation Polypeptides in the Mammalian Mitochondrial Membrane
Soung Jung Kim, Min-chul Kwon, Min Jeong Ryu, Hyo Kyun Chung, Surendar Tadi, Yong Kyung Kim, Jin Man Kim, Sang Hee Lee, Ji Hoon Park, Gi Ryang Kweon, Seung-Wook Ryu, Young Suk Jo, Chul-Ho Lee, Hideyuki Hatakeyama, Yu-ichi Goto, Yong-Hyeon Yim, Jongkyeong Chung, Young-Yun Kong
Although substantial progress has been made in understanding the mechanisms underlying the expression of mtDNA-encoded polypeptides, the regulatory factors involved in mitoribosome-mediated synthesis and simultaneous insertion of mitochondrial oxidative phosphorylation (OXPHOS) polypeptides into the inner membrane of mitochondria are still unclear. In the present study, disruption of the mouse Crif1 gene, which encodes a mitochondrial protein, resulted in a profound deficiency in OXPHOS caused by the disappearance of OXPHOS subunits and complexes in vivo. CRIF1 was associated with large mitoribosomal subunits that were located close to the polypeptide exit tunnel, and the elimination of CRIF1 led to both aberrant synthesis and defective insertion of mtDNA-encoded nascent OXPHOS polypeptides into the inner membrane. CRIF1 interacted with nascent OXPHOS polypeptides and molecular chaperones, e.g., Tid1. Taken together, these results suggest that CRIF1 plays a critical role in the integration of OXPHOS polypeptides into the mitochondrial membrane in mammals.