BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis
Journal Title
Science
Publication Type
Journal Article
Abstract
Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce mitochondrial outer membrane permeabilization, leading to cytochrome c release and activation of apoptotic caspases. In the absence of active caspases, mitochondrial DNA (mtDNA) triggers the innate immune cGAS/STING pathway, causing dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains unclear. We used live-cell lattice light-sheet microscopy to examine the mitochondrial network in mouse embryonic fibroblasts. We found that after BAK/BAX activation and cytochrome c loss, the mitochondrial network broke down and large BAK/BAX pores appeared in the outer membrane. These BAK/BAX macropores allowed the inner mitochondrial membrane to herniate into the cytosol, carrying with it mitochondrial matrix components, including the mitochondrial genome. Apoptotic caspases did not prevent herniation but dismantled the dying cell to suppress mtDNA-induced innate immune signaling.
Publisher
AAAS
WEHI Research Division(s)
Systems Biology And Personalised Medicine; Chemical Biology; Cell Signalling And Cell Death; Cancer And Haematology
PubMed ID
29472455
ARC Grants
ARC/160100063,
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-03-19 10:02:40
Last Modified: 2018-03-19 12:06:48
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