Kushnareva Y E, Polster B M, Sokolove P M, Kinnally K W, Fiskum G
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201, USA.
Arch Biochem Biophys. 2001 Feb 15;386(2):251-60. doi: 10.1006/abbi.2000.2201.
This study tested the hypothesis that mitochondrial precursor targeting peptides can elicit the release of cytochrome c from both liver and brain mitochondria by a mechanism distinct from that mediated by the classical, Ca2+-activated permeability transition pore. Human cytochrome oxidase subunit IV signal peptide (hCOXIV1-22) at concentrations from 15 to 100 microM induced swelling, a decrease in membrane potential, and cytochrome c release in both types of mitochondria. Although cyclosporin A and bongkrekic acid were without effect, dibucaine, propanolol, dextran, and the uncoupler FCCP were each able to inhibit signal peptide-induced swelling and cytochrome c release. Adenylate kinase was coreleased with cytochrome c, arguing against a signal peptide-induced cytochrome c-specific pathway of efflux across the outer membrane. Taken together, the data indicate that a human mitochondrial signal peptide can evoke the release of cytochrome c from both liver and brain mitochondria by a unique permeability transition that differs in several characteristics from the classical mitochondrial permeability transition.
线粒体前体靶向肽可通过一种不同于经典的、Ca2+激活的通透性转换孔介导的机制，引发肝脏和脑线粒体中细胞色素c的释放。浓度为15至100微摩尔的人细胞色素氧化酶亚基IV信号肽（hCOXIV1-22）可诱导两种类型线粒体肿胀、膜电位降低以及细胞色素c释放。尽管环孢素A和邦克酸无作用，但丁卡因、普萘洛尔、右旋糖酐和解偶联剂FCCP均能抑制信号肽诱导的肿胀和细胞色素c释放。腺苷酸激酶与细胞色素c共同释放，这与信号肽诱导的细胞色素c通过外膜的特异性流出途径相悖。综上所述，数据表明人线粒体信号肽可通过一种独特的通透性转换引发肝脏和脑线粒体中细胞色素c的释放，这种通透性转换在几个特征上不同于经典的线粒体通透性转换。
