Role of intracellular trafficking mediators in mitochondria membrane dynamics

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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.