Figure 3.

Cardiolipin peroxidation destabilizes cardiolipin microdomains on the inner mitochondrial membrane (IMM) and disrupts supercomplexes. Cardiolipin (CL) is particularly vulnerable to oxidative damage because of its high content of unsaturated fatty acids. Peroxidation of the acyl chains alters the structure of cardiolipin (CLOOH) and prevents cardiolipin from aggregating into microdomains or rafts on the IMM. The breakdown of cardiolipin rafts abolishes cristae curvatures and disrupts the organization of respiratory complexes into higher order supercomplexes. Peroxidation of cardiolipin also reduces its affinity for cyt c (C) and sets the stage for cyt c release into the cytosol and apoptosis. IMS: intermembrane space.