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. 2012 Feb 10;7(2):e32029. doi: 10.1371/journal.pone.0032029

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Cheng et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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(a) The intrinsic pathway of apoptosis is depicted. Cytochrome c (cyt c), the mobile electron carrier between Complexes III and IV in the electron transport chain, is bound to cardiolipin (CL) on the inner mitochondrial membrane via both electrostatic and hydrophobic interactions. Cyt c has peroxidase activity and, in the presence of hydrogen peroxide, oxidizes CL to hydroperoxycardiolipin (CL-OOH). This mobilizes cyt c from the inner membrane and permits cyt c release following permeabilization of the outer membrane. (b) Mechanism of carbon monoxide (CO) inhibition of cyt c peroxidase is shown. CO diffuses across the outer mitochondrial membrane, binds to the cyt c-CL complex, and inhibits the cyt c peroxidase activity. This prevents oxidation of CL, mobilization of cyt c, cyt c release, and subsequent caspase activation.