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

许多对植物生存力至关重要的代谢过程发生在线粒体中。为了确保这个细胞器的功能根据细胞的要求仔细平衡，线粒体被紧密整合到不同的调控网络中。最近，我们描述了钙/钙调素对蛋白质输入到植物线粒体的水平上的TIM 23和TIM 22介导的内膜上的易位的影响。初步研究表明，TIM 23本身，即TIM 23复合物的中心孔，可能是钙信号的靶点。拟南芥基因组编码Tim 23的三个旁系同源物，命名为atTim 23 -1、atTim 23 -2和atTim 23 -3，并且初步研究已经显示atTim 23 -2结合钙调蛋白的能力，从而表明该蛋白作为钙/钙调蛋白调节TIM 23易位的潜在介体。该项目的目的是所有三个atTim 23的功能表征，以阐明其作用模式，特别关注线粒体蛋白输入的钙调节的联系。此外，将阐明线粒体的钙调节子的其他组分，例如TIM 22易位的钙调节的介体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质转运的分子基础，以促进未来对该过程适应不同环境或发育线索的研究。

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.