Mitochondrial intermembrane space

The mitochondrial intermembrane space is the compartment between the outer and inner mitochondrial lipid bilayers, including the spaces within cristae. It is separated from the mitochondrial matrix by the inner lipid bilayer. During oxidative phosphorylation, respiratory proton pumps transfer hydrogen ions from the mitochondrial matrix toward this compartment. Return through ATP synthase couples the resulting proton-motive force to ATP synthesis. The relevant stored energy includes both an electrical potential difference and a chemical concentration difference. ^[ref]

The compartment also contains cytochrome c, an electron carrier associated with the outer face of the inner lipid bilayer. Its release into the cytosol can contribute to apoptosis. In a cell-free study, depletion of cytochrome c reduced apoptotic activity and add-back restored it, connecting loss of compartmentalization to a new biochemical function. ^[ref]