Regulation of mitochondrial protein transport: Tim23 as a link to the calcium-signalling network in the cell

植物生存所必需的许多代谢过程都发生在线粒体中。为了确保这种细胞器的功能根据细胞的要求得到仔细的平衡，线粒体被紧密地整合到不同的调节网络中。我们最近在TIM23和TIM22介导的内膜转位水平上描述了钙/钙调蛋白对蛋白质进入植物线粒体的影响。初步研究表明，TIM23本身，即TIM23复合体的中心孔，可能是钙信号的靶点。拟南芥基因组编码TIM23的三个类似物，命名为atTim23-1、atTim23-2和atTim23-3，初步研究表明atTim23-2具有结合钙调蛋白的能力，从而表明该蛋白可能是钙/钙调蛋白调节TIM23易位的媒介。该项目的目的是研究这三个基因在Tim23‘S中的功能特征，以阐明它们的作用模式，特别是与线粒体蛋白输入的钙调控有关的机制。此外，还将阐明线粒体钙调节蛋白的其他成分，如TIM22易位的钙调节介质和钙信号的相应传感器。该提案的总体目标是了解钙调节线粒体蛋白运输的分子基础，以促进未来研究这一过程对不同环境或发育线索的适应。

Many metabolic processes essential for plant viability take place in mitochondria. To ensure that function of this organelle is carefully balanced in accordance with requirements of the cell, mitochondria are tightly integrated into diverse regulatory networks. We recently described an influence of calcium/calmodulin on protein import into plant mitochondria at the level of the TIM23 and TIM22 mediated translocation on the inner membrane. Preliminary studies indicate, that Tim23 itself, the central pore of the TIM23 complex, could be a target for the calcium signal. The Arabidopsis genome encodes three paralogues of Tim23, named atTim23-1, atTim23-2 and atTim23-3 and preliminary studies have shown the ability of atTim23-2 to bind calmodulin, thereby suggesting the protein as a potential mediator for calcium/calmodulin regulation of TIM23 translocation. Aim of the project is the functional characterization of all three atTim23’s in order to elucidate their mode of action with a special focus on a link to calcium regulation of mitochondrial protein import. Furthermore, additional components of the calcium regulon of mitochondria will be elucidated, such as the mediator of calcium regulation of TIM22 translocation and the respective sensors of the calcium signals. The overall aim of the proposal is to understand the molecular basis of calcium regulation of mitochondrial protein transport to facilitate future studies on the adaptation of this process to different environmental or developmental cues.