Fig. 6: Amphipathic motif assembly promotes endophilin B1 activity at outer-mitochondrial membranes (OMMs) and drives apoptosis.

a Center and side dimers colored in the consensus map and a cartoon representation. Three potential forms of helical scaffolds with different orientations of H0. b Upon binding to a membrane that does not contain cardiolipin, endophilin B1 oligomerizes end-to-end (i) to form helical scaffolds that enforce membrane tubulation (ii). c Following apoptotic stimuli (i), cardiolipin (a non-bilayer lipid that induces negative curvature) migrates to the OMM (ii). The inner mitochondrial membrane (IMM) is destabilized leading to cytochrome-c (Cyt-c) dissociation. Endophilin B1 binds the OMM and oligomerizes side-to-side into circular scaffolds that cause local negative curvature and further clustering of cardiolipin (iii). Bax and other co-factors bind cardiolipin-rich sites (iv). Bax oligomerization induces leakage of Cyt-c from the intermembrane space (v), which triggers a proteolytic cascade, culminating in cell death. Created in BioRender. Thorlacius, A. (2025) https://BioRender.com/q66x841.