Ana J. García-Sáez

TL;DR: How microscopy approaches applied to model membranes are used to understand the intrinsic apoptotic pathway involving MOMP is discussed, which reveals interesting features like the role of membrane in altering the affinity of Bcl-2 proteins, Bax and Bak proAPoptotic activity, mechanistic differences between pro- and antiapoptotic members, and the critical helices involved in pore formation by Bax.

TL;DR: In this paper , the role of the mitochondria calcium homeostasis in the development of colorectal cancer (CRC) was examined and curcumin and pharmacological compounds induced the inhibition of NCLX-mediated mitochondrial calcium (mtCa2+) extrusion.

Abstract: Equinatoxin II (EqtII) and Fragaceatoxin C (FraC) are pore-forming toxins (PFTs) from the actinoporin family that have enhanced membrane affinity in the presence of sphingomyelin (SM) and phase coexistence in the membrane. However, little is known about the effect of these proteins on the nanoscopic properties of membrane domains. Here, we used combined confocal microscopy and force mapping by atomic force microscopy to study the effect of EqtII and FraC on the organization of phase-separated phosphatidylcholine/SM/cholesterol membranes. To this aim, we developed a fast, high-throughput processing tool to correlate structural and nano-mechanical information from force mapping. We found that both proteins changed the lipid domain shape. Strikingly, they induced a reduction in the domain area and circularity, suggesting a decrease in the line tension due to a lipid phase height mismatch, which correlated with proteins binding to the domain interfaces. Moreover, force mapping suggested that the proteins affected the mechanical properties at the edge, but not in the bulk, of the domains. This effect could not be revealed by ensemble force spectroscopy measurements supporting the suitability of force mapping to study local membrane topographical and mechanical alterations by membranotropic proteins.

TL;DR: In this paper, the structural and functional characterization of PFPs at individual vesicle and cell level is discussed, and the development of high-resolution and single-molecule imaging techniques allows the analysis of the structural organization of protein oligomers and pore entities in lipid membranes.

TL;DR: Interactions within the Bcl-2 protein network in solution and membranes are quantified, and membrane recruitment, preference of interaction partners and the consequences for Bax activation and inhibition are addressed.