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Abstract:
Apoptosis is a form of programmed cell death that plays an important role in key biological processes like development of organisms, the correct functioning of the immune system, and the maintenance of the cellular homeostasis. Dysregulation in the apoptotic pathway leads to diseases like cancer or neurodegenerative disorders. The proteins of the B-cell lymphoma 2 (Bcl-2) family are key regulators of mitochondrial outer membrane permeabilization (MOMP) during apoptosis, which is a critical step in the cell's commitment to death. However, their mechanism of action is still under intense investigation. Here, we discuss how microscopy approaches applied to model membranes are used to understand the intrinsic apoptotic pathway involving MOMP.
We describe how model membranes mimicking the outer mitochondrial membrane (LUVs, GUVs, SLB) are used to understand the mechanism of Bcl-2-mediated apoptosis using state-of-the-art techniques like atomic force microscopy and fluorescence correlation spectroscopy. These studies have revealed 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.
