Module 5: Figure OPA1 and mitochondrial cristae remodelling
OPA1 remodelling of mitochondrial cristae.
An oligomeric complex between integral membrane OPA1 and soluble OPA1, which is formed by presenilin-associated rhomboid-like (PARL) protease, forms a barrier across the opening of the cristae. Following redox stress, the increase in reactive oxygen species (ROS) such as superoxide (O2.-), has two effects; it causes peroxidation of cardiolipin to release cytochrome c (Module 5: Figure cardiolipin) and it remodels the organization of the cristae by disrupting the OPA1 oligomeric barrier to allow cytochrome c to diffuse through the Bax/Bak channel where it can trigger apoptosis. Opening up the inside of the cristae also allows Ca2+ greater access to the Ca2+ uniporters and the resulting increase in its concentration in the matrix enhances mitochondrial metabolism and this will increase ROS formation causing further mitochondrial damage.