Sztul E S, Chu T W, Strauss A W, Rosenberg L E
Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510.
J Biol Chem. 1988 Aug 25;263(24):12085-91.
The mitochondrial matrix enzyme malate dehydrogenase (MDH) is synthesized on cytoplasmic polysomes as a larger precursor (pMDH) with an NH2-terminal leader peptide of 24 amino acids. Import of in vitro synthesized MDH into mitochondria results in formation of the mature-sized subunit. We report here that the conversion of pMDH to mMDH occurs via two distinct cleavage events within the leader peptide. First, pMDH is cleaved to an intermediate form (iMDH) of MDH. Conversion of the precursor to the intermediate form is catalyzed by a protease localized to the mitochondrial matrix. The cleavage of pMDH to iMDH involves the removal of 15 amino acids from the NH2 terminus of the pMDH leader peptide. The iMDH is subsequently cleaved, also by a matrix protease, to mature MDH in a reaction which is O-phenanthroline-sensitive. Cleavage to iMDH and to mature MDH occurs prior to completion of translocation of the MDH polypeptide chain into the mitochondrial matrix.
线粒体基质酶苹果酸脱氢酶（MDH）在细胞质多核糖体上作为一种更大的前体（pMDH）合成，该前体带有一个24个氨基酸的NH2末端前导肽。体外合成的MDH导入线粒体后会形成成熟大小的亚基。我们在此报告，pMDH向mMDH的转化是通过前导肽内两个不同的切割事件发生的。首先，pMDH被切割成MDH的中间形式（iMDH）。前体向中间形式的转化由定位于线粒体基质的蛋白酶催化。pMDH切割成iMDH涉及从pMDH前导肽的NH2末端去除15个氨基酸。随后，iMDH也被一种基质蛋白酶切割成成熟的MDH，该反应对邻菲罗啉敏感。切割成iMDH和成熟MDH发生在MDH多肽链转运到线粒体基质完成之前。
