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TitleMolecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis.
Journal, issue, pagesElife, Vol. 8, Year 2019
Publish dateFeb 4, 2019
AuthorsNicholas R Ader / Patrick C Hoffmann / Iva Ganeva / Alicia C Borgeaud / Chunxin Wang / Richard J Youle / Wanda Kukulski /
PubMed AbstractDuring 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 ...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).
External linksElife / PubMed:30714902 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-4483:
Correlative FM and ET of GFP-Bax in HeLa cells
Method: EM (tomography)

EMDB-4484:
Correlative FM and ET of GFP-Bax in HCT116 cells
Method: EM (tomography)

EMDB-4486:
Correlative FM and cryo-ET of GFP-Bax in HeLa cells
Method: EM (tomography)

EMDB-4490:
cryo-ET of cryo-FIB milled HeLa cells overexpressing GFP-Bax
Method: EM (tomography)

EMDB-4491:
cryo-ET of cryo-FIB milled HeLa cell
Method: EM (tomography)

EMDB-4492:
cryo-ET of cryo-FIB milled Bax/Bak double knockout HCT116 cells stably expressing GFP-Bax
Method: EM (tomography)

Source
  • Homo sapiens (human)

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