Role of intracellular trafficking mediators in mitochondria membrane dynamics

细胞内运输介质在线粒体膜动力学中的作用

• 批准号: 386757-2010
• 负责人: Simmen, Thomas
• 金额: $ 2.4万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Group
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=485501
• 关键词: Role; intracellular; trafficking; mediators; mitochondria

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.

分泌消耗大量的能量来制造和运输待分泌的蛋白质。在大多数细胞中，线粒体为这种机制提供了大量能量。由于这种联系，我们假设分泌蛋白的细胞内运输是线粒体结构，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，特别是一类称为Rab蛋白的小贩运调节剂。该家族的蛋白质水解GTP以赋予细胞内运输步骤方向性，因此，特异性Rab与许多已知的细胞内运输步骤相关。我们的初步结果表明，至少有2个Rabs（Rab 32和Rab 38）确实调节线粒体膜动力学，因为它们的非活性形式导致细胞核周围线粒体的崩溃及其融合。我们假设，其他Rabs同样影响线粒体功能的这一方面。为了继续我们的计划，我们将继续筛选其他类别的运输调节剂，如网格蛋白衔接子和ADP-核糖基化因子（ARF）在未来。对于这个延续，我们已经确定了线粒体膜动力学中的衔接子相关的外套复合物的参与。