Cardiolipin: setting the beat of apoptosis.
Cardiolipin (CL) is a mitochondria-specific phospholipid which is known to be intimately linked with the mitochondrial bioenergetic machinery. Accumulating evidence now suggests that this unique lipid also has active roles in several of the mitochondria-dependent steps of apoptosis. CL is closely associated with cytochrome c at the outer leaflet of the mitochondrial inner membrane. This interaction makes the process of cytochrome c release from mitochondria more complex than previously assumed, requiring more than pore formation in the mitochondrial outer membrane. While CL peroxidation could be crucial for enabling cytochrome c dissociation from the mitochondrial inner membrane, cytochrome c itself catalyzes CL peroxidation. Moreover, peroxy-CL directly activates the release of cytochrome c and other apoptogenic factors from the mitochondria. CL is also directly involved in mitochondrial outer membrane permeabilization by enabling docking and activation of pro-apoptotic Bcl-2 proteins. It appears therefore that CL has multiple roles in apoptosis and that CL metabolism contributes to the complexity of the apoptotic process.
Gonzalvez
François
F
Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, United Kingdom.
Gottlieb
Eyal
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D018384:Oxidative Stress
D051023:BH3 Interacting Domain Death Agonist Protein; D002308:Cardiolipins; D045304:Cytochromes c