The role of the outer mitochondrial membrane protein porin in cell death and ageing

The Outer Mitochondrial Membrane (OMM) contains channels to reulate metabolic flux, such as the Voltage-Dependent Anion Channal (VDAC) also referred to as porin in Saccharomyces cerevisiae. Porin has been reported to play a role in apoptosis and oxidative stress, but surprisingly little is known about the role of VDAC in mitochondrial morphology, mitophagy, autophagy or ER-mitochondria conditions (The ER-mitochondoria encounter structure, ERMES). We present evidence through fluorescence microscopy that porin1 is associated with the ERMES complex and that its deletion results in aggregation of mitochondria that mimics the loss of ERMES components. This aggregation is associated with a loss of respiration, reduced capacity for autophagy, an increase in peroxisome number and elevated necrosis, elucidated through respirometry assays, western blots and flow cytometry. We have also found that overexpression of porin leads to activation of the cell wall integrity pathway, flocculation and cavuole fragmentation. Our experieents suggest that porin plays a critical role in the maintenance of mitochondrial function and the regulation of several important signalling mechanisms. These functions may be linked to as yet undefined roles for porin in lipid metabolism and the assembly of stress regulatory complexes on the mitochondrial surface.