Ott Martin, Norberg Erik, Walter Katharina M, Schreiner Patrick, Kemper Christian, Rapaport Doron, Zhivotovsky Boris, Orrenius Sten
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
J Biol Chem. 2007 Sep 21;282(38):27633-9. doi: 10.1074/jbc.M703155200. Epub 2007 Jul 16.
Cytochrome c release from mitochondria is a key event in apoptosis signaling that is regulated by Bcl-2 family proteins. Cleavage of the BH3-only protein Bid by multiple proteases leads to the formation of truncated Bid (tBid), which, in turn, promotes the oligomerization/insertion of Bax into the mitochondrial outer membrane and the resultant release of proteins residing in the intermembrane space. Bax, a monomeric protein in the cytosol, is targeted by a yet unknown mechanism to the mitochondria. Several hypotheses have been put forward to explain this targeting specificity. Using mitochondria isolated from different mutants of the yeast Saccharomyces cerevisiae and recombinant proteins, we have now investigated components of the mitochondrial outer membrane that might be required for tBid/Bax-induced cytochrome c release. Here, we show that the protein translocase of the outer mitochondrial membrane is required for Bax insertion and cytochrome c release.
细胞色素c从线粒体的释放是凋亡信号传导中的关键事件，该过程受Bcl-2家族蛋白调控。多种蛋白酶对仅含BH3结构域的蛋白Bid进行切割会导致截短型Bid（tBid）的形成，而tBid反过来又会促进Bax寡聚化/插入线粒体外膜，并导致膜间隙蛋白的释放。Bax是一种存在于细胞质中的单体蛋白，通过一种未知机制被靶向运输到线粒体。已经提出了几种假说来解释这种靶向特异性。我们利用从酿酒酵母不同突变体中分离得到的线粒体和重组蛋白，研究了tBid/Bax诱导的细胞色素c释放可能所需的线粒体外膜成分。在此，我们表明线粒体外膜的蛋白质转运酶是Bax插入和细胞色素c释放所必需的。
