Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/121707
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Type: Journal article
Title: BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis
Author: McArthur, K.
Whitehead, L.
Heddleston, J.
Li, L.
Padman, B.
Oorschot, V.
Geoghegan, N.
Chappaz, S.
Davidson, S.
Chin, H.
Lane, R.
Dramicanin, M.
Saunders, T.
Sugiana, C.
Lessene, R.
Osellame, L.
Chew, T.
Dewson, G.
Lazarou, M.
Ramm, G.
et al.
Citation: Science, 2018; 359(6378):883-+
Publisher: American Association for the Advancement of Science
Issue Date: 2018
ISSN: 0036-8075
1095-9203
Statement of
Responsibility: 
Kate McArthur, Lachlan W. Whitehead, John M. Heddleston, Lucy Li, Benjamin S. Padman ... Benjamin T. Kile ... et al.
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.
Keywords: Mice, Inbred C57BL
Rights: © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
RMID: 1000001806
DOI: 10.1126/science.aao6047
Grant ID: http://purl.org/au-research/grants/arc/FT160100063
http://purl.org/au-research/grants/arc/LE120100090
http://purl.org/au-research/grants/arc/LE100100165
http://purl.org/au-research/grants/arc/DP16012176
http://purl.org/au-research/grants/nhmrc/361646
Appears in Collections:Genetics publications

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