Vögtle F-Nora, Wortelkamp Stefanie, Zahedi René P, Becker Dorothea, Leidhold Claudia, Gevaert Kris, Kellermann Josef, Voos Wolfgang, Sickmann Albert, Pfanner Nikolaus, Meisinger Chris
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Cell. 2009 Oct 16;139(2):428-39. doi: 10.1016/j.cell.2009.07.045.
Many mitochondrial proteins are synthesized with N-terminal presequences that are removed by specific peptidases. The N-termini of the mature proteins and thus peptidase cleavage sites have only been determined for a small fraction of mitochondrial proteins and yielded a controversial situation for the cleavage site specificity of the major mitochondrial processing peptidase (MPP). We report a global analysis of the N-proteome of yeast mitochondria, revealing the N-termini of 615 different proteins. Significantly more proteins than predicted contained cleavable presequences. We identified the intermediate cleaving peptidase Icp55, which removes an amino acid from a characteristic set of MPP-generated N-termini, solving the controversial situation of MPP specificity and suggesting that Icp55 converts instable intermediates into stable proteins. Our results suggest that Icp55 is critical for stabilization of the mitochondrial proteome and illustrate how the N-proteome can serve as rich source for a systematic analysis of mitochondrial protein targeting, cleavage and turnover.
许多线粒体蛋白在合成时带有N端前序列，这些前序列会被特定的肽酶去除。仅对一小部分线粒体蛋白确定了成熟蛋白的N端以及肽酶切割位点，这导致主要线粒体加工肽酶（MPP）的切割位点特异性存在争议。我们报告了对酵母线粒体N蛋白质组的全面分析，揭示了615种不同蛋白质的N端。含有可切割前序列的蛋白质比预测的要多得多。我们鉴定出中间切割肽酶Icp55，它从MPP产生的一组特征性N端中去除一个氨基酸，解决了MPP特异性的争议情况，并表明Icp55将不稳定的中间体转化为稳定的蛋白质。我们的结果表明Icp55对线粒体蛋白质组的稳定至关重要，并说明了N蛋白质组如何作为系统分析线粒体蛋白靶向、切割和周转的丰富来源。
