Role of intracellular trafficking mediators in mitochondria membrane dynamics

分泌需要消耗大量的能量来制造和运输要分泌的蛋白质。在大多数细胞中，这种机制的大量能量是由线粒体提供的。由于这种联系，我们假设分泌蛋白在细胞内的运输是线粒体结构、新陈代谢和分布的决定因素。在这项研究计划中，我们的目标是干扰各种类型的贩运分子，特别是一类被称为RAB蛋白的小型贩运调节分子。该家族的蛋白质能降解GTP，使细胞内转运步骤具有方向性，因此，特定的RAB与许多已知的细胞内转运步骤有关。我们的初步结果表明，至少有2个RABS(Rab32和Rab38)确实调节线粒体膜动力学，因为它们的不活跃形式导致细胞核周围线粒体的崩溃和它们的融合。我们假设其他RAB类似地影响线粒体功能的这一方面。为了继续我们的计划，我们将在未来继续筛选其他类别的贩运调节因子，如网状蛋白适配器和ADP核糖化因子(ARF)。为此，我们已经确定了适配器相关的辅酶复合体在线粒体膜动力学中的参与。

Secretion consumes a lot of energy for the manufacture and the transport of proteins to be secreted. In most cells, a lot of energy for this mechanism is provided by the mitochondria. Because of this link, we hypothesize that intracellular trafficking of secretory proteins is a determinant of mitochondria structure, metabolism and distribution. In this research program, we aim to interfere with various classes of trafficking molecules and in particular a class of small trafficking regulators called Rab proteins. The proteins of this family hydrolyze GTP to confer directionality to intracellular trafficking steps and thus, specific Rabs are associated with many known intracellular trafficking steps. Our preliminary results show that at least 2 Rabs (Rab32 and Rab38) indeed modulate mitochondria membrane dynamics, since their inactive forms lead to a collapse of mitochondria around the nucleus and their fusion. We hypothesize that other Rabs similarly influence this aspect of mitochondria function. For the continuation of our program, we will proceed with the screening of other classes of trafficking regulators such as clathrin adaptors and ADP-ribosylation factors (ARFs) in the future. For this continuation, we have already determined the involvement of the adaptor-related coatomer complex in mitochondria membrane dynamics.