Characterization of Mmp37p, a Saccharomyces cerevisiae mitochondrial matrix protein with a role in mitochondrial protein import
Characterization of Mmp37p, a Saccharomyces cerevisiae mitochondrial matrix protein with a role in mitochondrial protein import
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DOI：
10.1091/mbc.e06-04-0366
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发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Long, Roy M.
中科院分区：
文献类型：
--
作者：
Gallas, Michelle R.;Dienhart, Mary K.;Long, Roy M.
许多线粒体蛋白由核基因编码，在细胞质中翻译后，分别通过外膜和内膜（TOM 和 TIM 复合物）中的转位酶输入。在这里，我们报告了线粒体蛋白 Mmp37p (YGR046w) 的表征，并证明了它参与蛋白质输入线粒体的过程。删除 MMP37 的单倍体细胞是可行的，但表现出对温度敏感的生长表型，并且在缺乏线粒体 DNA 的情况下是无法生存的。 Mmp37p 位于线粒体基质中，与内膜外围相连。我们表明，Mmp37p 在通过 TIM23-PAM 复合物跨线粒体内膜的蛋白质易位中发挥作用，并进一步证明，含有紧密折叠结构域且紧邻其线粒体靶向序列的底物在线粒体输入方面表现出对 Mmp37p 的特殊依赖性。前蛋白的预先展开，或靶向信号和紧密折叠结构域之间区域的延伸，减轻了它们对 Mmp37p 的依赖性。此外，有证据表明 Mmp37 可能影响 TIM23 复合物的组装状态。基于这些发现，我们假设 Mmp37p 的存在增强了 TIM23 基质输入途径的早期阶段，以确保传入的前蛋白与 mtHsp70p/PAM 复合物的接合，这是驱动前蛋白展开并完全易位到基质中所必需的步骤。
Many mitochondrial proteins are encoded by nuclear genes and after translation in the cytoplasm are imported via translocases in the outer and inner membranes, the TOM and TIM complexes, respectively. Here, we report the characterization of the mitochondrial protein, Mmp37p (YGR046w) and demonstrate its involvement in the process of protein import into mitochondria. Haploid cells deleted of MMP37 are viable but display a temperature-sensitive growth phenotype and are inviable in the absence of mitochondrial DNA. Mmp37p is located in the mitochondrial matrix where it is peripherally associated with the inner membrane. We show that Mmp37p has a role in the translocation of proteins across the mitochondrial inner membrane via the TIM23-PAM complex and further demonstrate that substrates containing a tightly folded domain in close proximity to their mitochondrial targeting sequences display a particular dependency on Mmp37p for mitochondrial import. Prior unfolding of the preprotein, or extension of the region between the targeting signal and the tightly folded domain, relieves their dependency for Mmp37p. Furthermore, evidence is presented to show that Mmp37 may affect the assembly state of the TIM23 complex. On the basis of these findings, we hypothesize that the presence of Mmp37p enhances the early stages of the TIM23 matrix import pathway to ensure engagement of incoming preproteins with the mtHsp70p/PAM complex, a step that is necessary to drive the unfolding and complete translocation of the preprotein into the matrix.