Published in Science Advances: Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis
2023-06-08
Luke Clifton, Hanna P. Wacklin-Knecht, Jörgen Ådén, Ameeq Ul Mushtaq, Tobias Sparrman, Gerhard Gröbner, Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore information to initiate apoptosis, Science Advances, DOI 10.1126/sciadv.adg7940 http://www.science.org/doi/10.1126/sciadv.adg7940
Abstract: Apotosis is an essential process tightly regulated by the Bcl-2 protein family where proapoptotic Bax triggers cell death by perforating the mitochondrial outer membrane. Although intensively studied, the molecular mechanism by which these proteins create apoptotic pores remains elusive. Here, we show that Bax creates pores by extracting lipids from outer mitochondrial membrane mimics by formation of Bax/lipid clusters that are deposited on the membrane surface. Time-resolved neutron reflectometry and Fourier transform infrared spectroscopy revealed two kinetically distinct phases in the pore formation process, both of which were critically dependent on cardiolipin levels. The initially fast adsorption of Bax on the mitochondrial membrane surface is followed by a slower formation of pores and Bax-lipid clusters on the membrane surface. Our findings provide a robust molecular understanding of mitochondrial membrane perforation by cell-killing Bax protein and illuminate the initial phases of programmed cellular death.
Related links ESS, STFC UKRI:
https://www.isis.stfc.ac.uk/Pages/Understanding-programmed-cell-death.aspx
https://www.isis.stfc.ac.uk/Pages/Understanding-programmed-cell-death.aspx
https://www.ukri.org/news/details-of-cellular-process-which-stops-cancer-developing-revealed/