Eilers M, Endo T, Schatz G
Biocenter, University of Basel, Switzerland.
J Biol Chem. 1989 Feb 15;264(5):2945-50.
Acidic phospholipids such as cardiolipin partially unfold an artificial precursor protein which consists of a mitochondrial presequence fused to mouse dihydrofolate reductase (Endo, T., and Schatz, G. (1988) EMBO J. 7, 1153-1158). We now show that import of this precursor protein into isolated yeast mitochondria is blocked by adriamycin, a drug binding to cardiolipin and other acidic phospholipids. This inhibition is lessened if the precursor's dihydrofolate reductase moiety is labilized by point mutations; inhibition is abolished altogether if the "wild-type" precursor is presented to mitochondria in a urea-denatured state. These and other observations suggest that adriamycin interferes with the generation of a translocation-competent, loose structure of the precursor protein. They imply that acidic phospholipids such as cardiolipin participate, directly or indirectly, in the translocation of this fusion protein into isolated mitochondria.
酸性磷脂如心磷脂可使一种人工前体蛋白部分展开，该前体蛋白由与小鼠二氢叶酸还原酶融合的线粒体前导序列组成（远藤，T.，和沙茨，G.（1988年）《欧洲分子生物学组织杂志》7卷，1153 - 1158页）。我们现在表明，将这种前体蛋白导入分离的酵母线粒体被阿霉素阻断，阿霉素是一种与心磷脂和其他酸性磷脂结合的药物。如果前体的二氢叶酸还原酶部分因点突变而不稳定，这种抑制作用会减弱；如果将“野生型”前体以尿素变性状态呈现给线粒体，抑制作用则完全消除。这些以及其他观察结果表明，阿霉素干扰了具有转位能力的前体蛋白松散结构的形成。这意味着酸性磷脂如心磷脂直接或间接地参与了这种融合蛋白向分离线粒体的转位。
