How might OPA1 sequester cytochrome c inside cristae?
The OPA1 protein has been found to be responsible for closing the sac in which cytochrome c is sequestered. A new structural alteration that has been observed during apoptosis by several independent groups is the disassembly of OPA1 protein complexes that causes remodelling of cristae and crista junctions. During tBid-treatment, oligomerised OPA1 complexes disappear rapidly, leaving only the monomeric form. This event requires the presence of either Bak or Bax, but does not require the activation of Bak, as shown by a combination of pharmacological inhibition of Bak oligomerisation and genetic manipulation. Remarkably, the Bax/Bak dependent events at the inner membrane (OPA1 complex disassembly and crista remodelling) can be uncoupled from Bax/Bak-dependent events at the outer membrane (Bak oligomerisation and outer membrane permeabilisation). The expression of a disassembly-resistant mutant OPA1 blocks both the full release of cytochrome c and apoptosis. Another piece to the puzzle is
