Cell Biology, Technische Universität Kaiserslautern, 67663 Kaiserslautern, Germany.
Molecular Evolution, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
Mol Biol Cell. 2020 Nov 15;31(24):2657-2668. doi: 10.1091/mbc.E20-08-0524. Epub 2020 Sep 30.
Most mitochondrial proteins are synthesized as precursors that carry N-terminal presequences. After they are imported into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase (MPP). Using the mitochondrial tandem protein Arg5,6 as a model substrate, we demonstrate that MPP has an additional role in preprotein maturation, beyond the removal of presequences. Arg5,6 is synthesized as a polyprotein precursor that is imported into mitochondria and subsequently separated into two distinct enzymes. This internal processing is performed by MPP, which cleaves the Arg5,6 precursor at its N-terminus and at an internal site. The peculiar organization of Arg5,6 is conserved across fungi and reflects the polycistronic arginine operon in prokaryotes. MPP cleavage sites are also present in other mitochondrial fusion proteins from fungi, plants, and animals. Hence, besides its role as a "ticket canceller" for removal of presequences, MPP exhibits a second conserved activity as an internal processing peptidase for complex mitochondrial precursor proteins.
大多数线粒体蛋白作为带有 N 端前导序列的前体被合成。这些靶向信号在被线粒体加工肽酶（MPP）切割后，进入线粒体。我们使用线粒体串联蛋白 Arg5,6 作为模型底物，证明 MPP 在去除前导序列之外，在前体蛋白成熟中还有额外的作用。Arg5,6 作为多蛋白前体被合成，然后被导入线粒体，并随后分离成两种不同的酶。这种内部加工是由 MPP 完成的，它在 N 端和内部位点切割 Arg5,6 前体。Arg5,6 的特殊组织在真菌中是保守的，反映了原核生物中多顺反子的精氨酸操纵子。真菌、植物和动物的其他线粒体融合蛋白也存在 MPP 切割位点。因此，除了作为去除前导序列的“票取消器”的作用外，MPP 还表现出作为复杂线粒体前体蛋白的内部加工肽酶的第二个保守活性。
