期刊
SCIENCE
卷 359, 期 6378, 页码 883-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao6047
关键词
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资金
- Australian Federal Government Postgraduate Award [1077750, 1106471, 1078924, 1083077, 1016647, 1113577, 1113133, 1063008, 1117089]
- ARC Future Fellowship [160100063]
- ARC [DP16012176]
- Independent Research Institutes Infrastructure Support Scheme Grant from the Australian National Health and Medical Research Council (NHMRC) [361646]
- Australian Cancer Research Fund
- Victorian State Government Operational Infrastructure Support Grant
- Howard Hughes Medical Institute
- Gordon and Betty Moore Foundation
- Ramaciotti Foundation [CD11/1958]
- Australian Research Council [LE120100090, LE100100165]
- Australian Research Council [LE100100165, LE120100090] Funding Source: Australian Research Council
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.
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