Membrane Remodeling and Diffusion of Cytochrome C from a Geometrically Idealized Mitochondrial Crista

In healthy eukaryotic cells, mitochondria have an outer membrane that surrounds a complex inner membrane structure [7,8]. Cytochrome c is found in the space between the two membranes, the inter-membrane space, where it takes part in the electron transport process. Mitochondria interact with the cell in the process of apoptosis (programmed cell death). During apoptosis cytochrome c is released from the mitochondria into the cytoplasm. It is known that essentially all (more than 90%) of the cytochrome c inside of a mitochondrion is released to the cytosol in one to two minutes. The mechanism by which this release occurs is the subject of this paper. Structural transformations in the inner mitochondrial membrane have been observed during apoptosis [6]. We consider the hypothesis that such shape restructuring is required for the timely release of cytochrome c during apoptosis. The extent to which shape restructuring of the inner mitochondrial membrane could affect the timing of this release is the mathematical question that is examined. The quantitative model presented here simulates the diffusion of cytochrome c from within the inter-membrane space. The adsorption and chemisorption of cytochrome c onto the inner membrane and the tendency of cytochrome c to bind with other species in solution complicate the problem. These complications effectively move the cytochrome c into remote pools. While many of the rate constants between remote pools are presently unknown, this model considers the rate constants between cytochrome c and complex III and complex IV and their effect upon cytochrome c release and the need for membrane remodeling to produce diffusion times consistent with observed experimental data.