Proteolytic cleavage by the inner membrane peptidase (IMP) complex or Oct1 peptidase controls the localization of the yeast peroxiredoxin Prx1 to distinct mitochondrial compartments
Proteolytic cleavage by the inner membrane peptidase (IMP) complex or Oct1 peptidase controls the localization of the yeast peroxiredoxin Prx1 to distinct mitochondrial compartments
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DOI：
10.1074/jbc.m117.788588
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发表时间：
2017-10-13
影响因子：
4.8
通讯作者：
Netto, Luis E. S.
中科院分区：
文献类型：
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作者：
Gomes, Fernando;Palma, Flavio Romero;Netto, Luis E. S.
Yeast Prx1 是一种线粒体 1-Cys 过氧化还原蛋白，可催化内源产生的 H2O2 的还原。 Prx1 在胞质核糖体上合成为前蛋白，具有可裂解的 N 端前序列（线粒体靶向信号），但 Prx1 分布到不同线粒体亚区室的机制尚不清楚。在这里，我们提供了 Prx1 以下双重线粒体定位的直接证据：膜间隙中的可溶形式和与线粒体内膜弱相关的基质中的形式。我们发现 Prx1 分选到膜间空间可能涉及内膜脂质双层内蛋白质前体的释放，然后被内膜肽酶裂解。我们还发现，在导入基质室的过程中，Prx1 依次被线粒体加工肽酶和八肽氨肽酶 1 (Oct1) 裂解。 Oct1 从基质内的 Prx1 N 末端区域切割 8 个氨基酸残基，而不会干扰其体外过氧化物酶活性。值得注意的是，Oct1 对过氧化还原蛋白 (Prx) 蛋白的加工似乎是一个进化上保守的过程，因为当酵母 Oct1 在酿酒酵母中表达时，它可以裂解人类线粒体过氧化还原蛋白 Prx3。总而言之，Imp2 或 Oct1 对过氧化还原蛋白的处理可能代表控制 Prxs 定位到不同区室的系统，从而有助于各种线粒体氧化还原过程。
Yeast Prx1 is a mitochondrial 1-Cys peroxiredoxin that catalyzes the reduction of endogenously generated H2O2. Prx1 is synthesized on cytosolic ribosomes as a preprotein with a cleavable N-terminal presequence that is the mitochondrial targeting signal, but the mechanisms underlying Prx1 distribution to distinct mitochondrial subcompartments are unknown. Here, we provide direct evidence of the following dual mitochondrial localization of Prx1: a soluble form in the intermembrane space and a form in the matrix weakly associated with the inner mitochondrial membrane. We show that Prx1 sorting into the intermembrane space likely involves the release of the protein precursor within the lipid bilayer of the inner membrane, followed by cleavage by the inner membrane peptidase. We also found that during its import into the matrix compartment, Prx1 is sequentially cleaved by mitochondrial processing peptidase and then by octapeptidyl aminopeptidase 1 (Oct1). Oct1 cleaved eight amino acid residues from the N-terminal region of Prx1 inside the matrix, without interfering with its peroxidase activity in vitro. Remarkably, the processing of peroxiredoxin (Prx) proteins by Oct1 appears to be an evolutionarily conserved process because yeast Oct1 could cleave the human mitochondrial peroxiredoxin Prx3 when expressed in Saccharomyces cerevisiae. Altogether, the processing of peroxiredoxins by Imp2 or Oct1 likely represents systems that control the localization of Prxs into distinct compartments and thereby contribute to various mitochondrial redox processes.