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https://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.W. Heddleston, J.M. Li, L. Padman, B.S. Oorschot, V. Geoghegan, N.D. Chappaz, S. Davidson, S. Chin, H.S. Lane, R.M. Dramicanin, M. Saunders, T.L. Sugiana, C. Lessene, R. Osellame, L.D. Chew, T.L. 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. |
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 |
Published version: | http://dx.doi.org/10.1126/science.aao6047 |
Appears in Collections: | Aurora harvest 4 Genetics publications |
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