New Channels in the Outer Mitochondrial Membrane

Abstract

Mitochondria are the power stations of eukaryotic cells. Beside this they play essential roles for the metabolism and physiology of cells and are a central point of apoptosis regulation. Mitochondria are also involved in calcium homeostasis.Due to endosymbiontic engulfment mitochondria are surrounded by two membranes. While the regulation of the metabolite flux across the inner membrane (IMM) is extensively characterised, it has been generally assumed that the outer membrane (OMM) functions only as a barrier for molecules larger than 3 kDa. But recent studies demonstrate that the metabolite flux between the cytosol and the different compartments of mitochondria is regulated at the level of the outer membrane.Three pore forming proteins are up to now known in the outer membrane. Two of them are essential and involved in protein transport and insertion into OMM. These are Tom40 and Sam50/Tob55. The third one is the non-essential metabolite pore VDAC (voltage-dependent anion channel). The none lethal phenotype of VDAC knockouts discloses that it is the sole metabolite conducting pore in the OMM and the presence of other non-identified channels in the OMM is very likely.The OMM proteome contains more than 112 proteins and only for less than 10 % of them the function is known. By electrophysiological screening of highly pure OMMvdac Δ vesicles it was possible to identify at least four distinct membrane pores. In a first bioinformatical attempt using specific parameters like the isoelectric point or second structure prediction programs we identified eight potential channel candidate proteins.