When cytochrome c is released from the intermembrane space of mitochondria into the cytoplasm, caspases in the cytoplasm become activated and they initiate apoptosis. Besides cytochrome c, other proteins that normally reside in the intermembrane space are also released into the cytoplasm, one of them is Smac which inhibits inhibitors of apoptosis. Controlling the permeability of the outer membrane of mitochondria is therefore crucial to the survival of the cell. Which event trigger the permeability to increase so that apoptosis follows?
This paper finds that first, Bax and Bak are recruited to the surface of mitochondria. This then activates OMA1, an m-AAA inner membrane protease that is responsible for cleavage of the long isoforms of OPA1. OPA1 can shape cristae, so when it is cleaved the cristae will remodel and this is presumably what makes it possible for cytochrome c to be released.
- Bax/Bak oligomerize on the mitochondrial surface
- This oligomerization somehow changes the inner membrane structure and activates OMA1, an inner membrane m-AAA protease.
- OMA1 cleaves L-OPA1
- A change in the ratio of long to short isoforms of OPA1 influences cristae structure, so the cristae start remodelling
- cytochrome c is released