File:Models of Mitochondrial Membrane Permeabilization.jpg
Different Models of Mitochondrial Membrane Permeabilization (MMP)
Large pores formed by the oligomerization of proapoptotic Bcl-2 proteins (e.g., Bax, Bak) and/or the voltage-dependent anion channel (VDAC) may promote selectively mitochondrial outer membrane permeabilization (MOMP).
In this case, specific intermembrane space (IMS) proteins are liberated in the cytosol, but the mitochondrial transmembrane potential (Δψm) is (at least initially) retained (A,B). On the contrary, some proapoptotic stimuli, such as calcium (Ca2+) overload, reactive oxygen species (ROS), and the lipid second messenger ceramide, favor MMP by inducing the permeabilization of the inner mitochondrial membrane (IM) via the activation of the permeability transition pore complex (PTPC).
When the PTPC opens, Δψm is immediately lost and an unregulated entry of solutes and water into the mitochondrial matrix occurs. This results in the osmotic swelling of mitochondria, followed by rupture of both mitochondrial membranes and the unspecific release into the cytosol of IMS proteins (A,C) (please refer to the sections “MMP Regulation by Bcl-2 Family Proteins” and “MMP Regulation by the PTPC” for additional details).
Notably, antiapoptotic proteins from the Bcl-2 family play a role in both models. AIF, apoptosis-inducing factor; ANT, adenine nucleotide translocase; CK, creatine kinase; CypD, cyclophilin D; Cyt c, cytochrome c; HK, hexokinase; OXPHOS, oxidative phosphorylation complexes; PBR, peripheral-type benzodiazepine receptor.
PLoS Pathog. 2008 May; 4(5): e1000018. Published online 2008 May 30. doi: 10.1371/journal.ppat.1000018.
Galluzzi 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 credited.
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|current||13:47, 29 March 2009||478 × 328 (89 KB)||S8600021||Figure 2 Different Models of Mitochondrial Membrane Permeabilization (MMP). Large pores formed by the oligomerization of proapoptotic Bcl-2 proteins (e.g., Bax, Bak) and/or the voltage-dependent anion channel (VDAC) may promote selectively mitochondrial|
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