Bax assembly into rings and arcs in apoptotic mitochondria is linked to membrane pores. (18th January 2016)

• Record Type: Journal Article
• Authors: Salvador‐Gallego, Raquel; Mund, Markus; Cosentino, Katia; Schneider, Jale; Unsay, Joseph; Schraermeyer, Ulrich; Engelhardt, Johann; Ries, Jonas; García‐Sáez, Ana J
• Is Part Of: EMBO journal. Volume 35:Number 4(2016)
• Page Start: 389
• Page End: 401
• Publication Date: 2016-01-18
• Subjects: AFM -- apoptosis -- Bcl‐2 -- pore‐forming protein -- super‐resolution microscopy; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201593384
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Bax is a key regulator of apoptosis that, under cell stress, accumulates at mitochondria, where it oligomerizes to mediate the permeabilization of the mitochondrial outer membrane leading to cytochrome c release and cell death. However, the underlying mechanism behind Bax function remains poorly understood. Here, we studied the spatial organization of Bax in apoptotic cells using dual‐color single‐molecule localization‐based super‐resolution microscopy. We show that active Bax clustered into a broad distribution of distinct architectures, including full rings, as well as linear and arc‐shaped oligomeric assemblies that localized in discrete foci along mitochondria. Remarkably, both rings and arcs assemblies of Bax perforated the membrane, as revealed by atomic force microscopy in lipid bilayers. Our data identify the supramolecular organization of Bax during apoptosis and support a molecular mechanism in which Bax fully or partially delineates pores of different sizes to permeabilize the mitochondrial outer membrane. Synopsis: Super‐resolution analyses show that Bax oligomerizes into lines, arcs, and rings to mediate mitochondrial outer membrane permeabilization during apoptosis. Active Bax oligomerizes into full rings, lines, and arcs in apoptotic mitochondria. Rings and arc‐shaped Bax assemblies are able to partially or completely line pores in lipid membranes. Abstract : Super‐resolution analyses show that Bax oligomerizes into lines, arcs, and rings to mediate mitochondrial outer membrane permeabilization during apoptosis.