Their experiments on artificial membrane systems showed that the Bax protein initially is inserted into the membrane as a single molecule. Once inserted, this monomer instantly teams up with another Bax molecule to form a stable complex, the so-called 'Bax dimer'. From these dimers larger complexes are formed. "Surprisingly, Bax complexes have no standard size, but we observed a mixture of different-sized Bax species," says Dr. Katia Cosentino, a member of Professor García-Sáez team, "and these species are mostly based on dimer units." These Bax complexes ultimately form the pores through which Cytochrome c exits the mitochondrial membrane.
The process of pore formation is finely controlled by other proteins. Some enable the assembly of Bax-elements, while others induce their dismantling. "The differing size of the Bax complexes in the pore formation is likely part of the reason why earlier investigations on pore formation conveyed in contradictory results", explains Katia Cosentino. The researchers can now make some initial recommendations for medical intervention in the apoptotic process: In order to promote cell suicide, it should be enough to initiate the first step by activating Bax proteins – because the subsequent steps will then happen automatically. Conversely, from these new insights it can be concluded that apoptosis may be prevented when drugs dissolve the Bax dimers.
Ana García-Sáez has been a professor in Tübingen since 2013 and received an ERC Starting Grant in 2012. She had gained her PhD at the University in Valencia, Spain, where she studied biochemistry and chemistry. She completed her post-doc work at the TU Dresden in Germany, where she received a Marie Curie Intra European fellowship. Besides being a professor in Tübingen, she is a research group leader at the Max Planck Institute for Intelligent Systems in Stuttgart.
(© University of Tübingen, AcademiaNet)