Although membrane pores are induced by the formation of BAX complexes at membrane, the pore size depends critically on lipid composition.
Role of Cardiolipin in the BAX Activation
Lipid-dependent BAX oligomers
We identify the inactive versus active forms of membrane-associated BAX, only the latter of which can induce stable and large membrane pores that are sufficient in size to pass apoptogenic factors. We reveal that the presence of CL is crucial to promoting the association between BAX dimers, hence the active oligomers. Without the presence of CL, BAX dimers assemble into an inactive oligomer that lacks the ability to form stable pores in the membrane. This study suggests an important role of CL in determining the formation of active BAX oligomers.
One of the main topics in the Chiang Lab is about understanding the molecular details of how the BCL2 protein family regulates the mitochondria-dependent apoptosis. In particular, we are interested in the BAX-mediated cell death pathway.
Membrane protein & protein-membrane associated complexes
Our recent study reveals a complete solution structure of apoptotic BAX protein oligomer. The results suggest an alternative pathway of apoptosis in which BAX oligomer formation occurs prior to membrane insertion.