Molecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis.

Autor:	Ader NR; Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.; Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States., Hoffmann PC; Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom., Ganeva I; Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom., Borgeaud AC; Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom., Wang C; Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States., Youle RJ; Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States., Kukulski W; Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2019 Feb 04; Vol. 8. Date of Electronic Publication: 2019 Feb 04.
DOI:	10.7554/eLife.40712
Abstrakt:	During apoptosis, Bcl-2 proteins such as Bax and Bak mediate the release of pro-apoptotic proteins from the mitochondria by clustering on the outer mitochondrial membrane and thereby permeabilizing it. However, it remains unclear how outer membrane openings form. Here, we combined different correlative microscopy and electron cryo-tomography approaches to visualize the effects of Bax activity on mitochondria in human cells. Our data show that Bax clusters localize near outer membrane ruptures of highly variable size. Bax clusters contain structural elements suggesting a higher order organization of their components. Furthermore, unfolding of inner membrane cristae is coupled to changes in the supramolecular assembly of ATP synthases, particularly pronounced at membrane segments exposed to the cytosol by ruptures. Based on our results, we propose a comprehensive model in which molecular reorganizations of the inner membrane and sequestration of outer membrane components into Bax clusters interplay in the formation of outer membrane ruptures. Editorial Note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). Competing Interests: NA, PH, IG, AB, CW, WK No competing interests declared, RY Reviewing editor, eLife
Databáze:	MEDLINE
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