BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis-Reference-Cited by-同舟云学术

BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis

Published:2018-02-23 Issue:6378 Volume:359 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

McArthur Kate¹²³^ORCID,Whitehead Lachlan W.¹²^ORCID,Heddleston John M.⁴^ORCID,Li Lucy¹^ORCID,Padman Benjamin S.⁵^ORCID,Oorschot Viola⁶^ORCID,Geoghegan Niall D.¹²,Chappaz Stephane¹²³,Davidson Sophia¹^ORCID,San Chin Hui¹^ORCID,Lane Rachael M.³,Dramicanin Marija¹²,Saunders Tahnee L.³,Sugiana Canny³,Lessene Romina¹²,Osellame Laura D.⁵,Chew Teng-Leong⁴,Dewson Grant¹²,Lazarou Michael⁵,Ramm Georg⁵⁶^ORCID,Lessene Guillaume¹²⁷^ORCID,Ryan Michael T.⁵^ORCID,Rogers Kelly L.¹²^ORCID,van Delft Mark F.¹²^ORCID,Kile Benjamin T.¹²³^ORCID

Affiliation:

1. Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

2. Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.

3. Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.

4. Advanced Imaging Center, Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, USA.

5. Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.

6. Monash Ramaciotti Centre for Cryo Electron Microscopy, Monash University, Melbourne, Victoria, Australia.

7. Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia.

Abstract

The great escape Mitochondrial DNA (mtDNA) is a potent damage-associated molecular pattern that, if it reaches the cytoplasm or extracellular milieu, triggers innate immune pathways. mtDNA signaling has been implicated in a wide range of diseases; however, the mechanisms of mtDNA release are unclear, and the process has not been observed in real time thus far. McArthur et al. used live-cell lattice light-sheet microscopy to look at mtDNA release during intrinsic apoptosis. Activation of the pro-death proteins BAK and BAX resulted in the formation of large macro-pores in the mitochondrial outer membrane. These massive holes caused the inner mitochondrial membrane to balloon out into the cytoplasm, resulting in mitochondrial herniation. This process allowed the contents of the mitochondrial matrix, including mtDNA, to escape into the cytoplasm. Science , this issue p. eaao6047

Funder

National Health and Medical Research Council

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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