Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochrome c and Cardiolipin

Figure 1

Role of cardiolipin in cell homeostasis and apoptosis. (a) Under homeostatic conditions, cardiolipin (CL) facilitates the assembly of respiratory supercomplexes (brown arrows) and maintains a population of Cc bound to the inner mitochondrial membrane (IMM). The efficiency of electron transfer is high (thick red arrow). (b) Under apoptotic stimuli, procaspase-8 is recruited to CL-enriched microdomains in the outer mitochondrial membrane (OMM). The activation of caspase-8 involves cleavage of the BID proapoptotic factor into two domains, namely, the N-terminal (n-Bid) and C-terminal fragments (t-Bid). Dissociation of these two fragments is required for the interaction of t-Bid with CL. Then, t-Bid promotes the formation of mitochondrial pores by assembling BAX–BAK oligomers. At the same time, ROS production increases and Cc acts as a ROS scavenger and pseudoperoxidase. Cc peroxidase activity results in oxidation of CL acyl chains, to which the hemeprotein is anchored, freeing Cc from the IMM, facilitating its subsequent release into the cytosol upon OMM permeabilization. The efficiency of electron transfer is low (dashed red arrow). In addition, CL can be degraded in part, losing one of its acyl chains, giving rise to monolysocardiolipin (MLCL).

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