Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis.
Cardiolipin (CL) is a unique anionic phospholipid specific to the mitochondria. CL influences the activity of electron transport chain enzyme complexes as well as members of the Bcl-2 family. Interactions between Bcl-2 family members and other pro-apoptotic enzymes have been shown to be crucial for the transduction of the apoptotic signalling cascades during programmed cell death. Targeting of tBid to the mitochondria, which is necessary for Bax/Bak oligomerization and cristae remodelling, is dependent on the exposure of CL at contact sites between the inner and outer mitochondrial membranes. Also, the mobilization of cytochrome c, another key apoptotic event, is tightly regulated by the oxidative state of cardiolipin. Moreover, CL has been shown to be essential for translocation and autoprocessing of caspase-8 on the mitochondria after death receptor stimulation. Deficiencies in CL inhibit the formation of tBid and prevent apoptosis by removing an essential activation platform for the autoprocessing of caspase-8. It is now apparent that CL acts as a crucial signalling platform from which it orchestrates apoptosis by integrating signals from a variety of death inducing proteins.
Schug
Zachary T
ZT
Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, G61 1BD, UK.
Gottlieb
Eyal
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002308:Cardiolipins / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D002308:Cardiolipins