Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Biochemistry and Molecular Biology, and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing Michigan, 48824-1319, USA.
Sci Rep. 2017 Aug 16;7(1):8315. doi: 10.1038/s41598-017-08088-6.
ClpXP is the major protease in the mitochondrial matrix in eukaryotes, and is well conserved among species. ClpXP is composed of a proteolytic subunit, ClpP, and a chaperone-like subunit, ClpX. Although it has been proposed that ClpXP is required for the mitochondrial unfolded protein response, additional roles for ClpXP in mitochondrial biogenesis are unclear. Here, we found that Drosophila leucine-rich pentatricopeptide repeat domain-containing protein 1 (DmLRPPRC1) is a specific substrate of ClpXP. Depletion or introduction of catalytically inactive mutation of ClpP increases DmLRPPRC1 and causes non-uniform increases of mitochondrial mRNAs, accumulation of some unprocessed mitochondrial transcripts, and modest repression of mitochondrial translation in Drosophila Schneider S2 cells. Moreover, DmLRPPRC1 over-expression induces the phenotypes similar to those observed when ClpP is depleted. Taken together, ClpXP regulates mitochondrial gene expression by changing the protein level of DmLRPPRC1 in Drosophila Schneider S2 cells.
ClpXP 是真核生物线粒体基质中的主要蛋白酶，在物种间高度保守。ClpXP 由一个蛋白水解亚基 ClpP 和一个伴侣样亚基 ClpX 组成。虽然已经提出 ClpXP 是线粒体未折叠蛋白反应所必需的，但 ClpXP 在线粒体生物发生中的其他作用尚不清楚。在这里，我们发现果蝇富含亮氨酸的五肽重复结构域蛋白 1（DmLRPPRC1）是 ClpXP 的特异性底物。ClpP 的耗竭或催化活性突变的引入增加了 DmLRPPRC1，并导致线粒体 mRNA 的非均匀增加、一些未加工的线粒体转录本的积累以及线粒体翻译的适度抑制在果蝇 Schneider S2 细胞中。此外，DmLRPPRC1 的过表达诱导的表型类似于 ClpP 耗尽时观察到的表型。总之，ClpXP 通过改变果蝇 Schneider S2 细胞中 DmLRPPRC1 的蛋白水平来调节线粒体基因表达。
