7月20日,,Cell Metab雜志在線報(bào)道,線粒體蛋白CRIF1通過與新生的氧化磷酸化多肽及分子伴侶相互作用調(diào)節(jié)線粒體編碼的氧化磷酸化多肽的合成和插入線粒體內(nèi)膜過程,。
雖然對線粒體DNA編碼多肽表達(dá)機(jī)制的研究已經(jīng)取得了很大的進(jìn)展,參與線粒體核蛋白體介導(dǎo)的多肽合成和將線粒體氧化磷酸化(OXPHOS)多肽自發(fā)插入線粒體內(nèi)膜過程的調(diào)控因子目前還不清楚,。
在本研究中,,干擾編碼線粒體蛋白的小鼠Crif1基因表達(dá),可導(dǎo)致體內(nèi)因氧化磷酸化亞基和復(fù)合物消失所造成的氧化磷酸化的嚴(yán)重缺陷,。CRIF1與線粒體核蛋白體大亞基聯(lián)系在一起,,定位在靠近多肽輸出隧道的出口處,消除CRIF1的表達(dá)導(dǎo)致線粒體DNA編碼的氧化磷酸化新生多肽的異常合成和有缺陷地插入線粒體內(nèi)層膜,。CRIF1與新生的氧化磷酸化多肽及分子伴侶,,例如,Tid1,,相互作用,。
這些結(jié)果表明,CRIF1在哺乳動物氧化磷酸化多肽整合入線粒體膜的過程中發(fā)揮關(guān)鍵作用,。(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.