IMB Seminar Series – Professor Benjamin Kile – ‘Mitochondrial herniation and mtDNA release during cell death’
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- Mitochondrial herniation and mtDNA release during cell death
Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that oligomerise in the mitochondrial outer-membrane to induce permeabilization, leading to cytochrome-c efflux and activation of apoptotic caspases. Recent evidence indicates that, in the absence of active caspases, mitochondrial (mt) DNA triggers the innate immune cGAS/STING pathway, causing dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains unclear, particularly since BAK/BAX are not thought to permeabilize the organelle’s inner membrane. Using live-cell lattice light-sheet, 3D-structured illuminated and immunogold electron microscopy, we have now shown that BAK/BAX activation leads to mitochondrial inner-membrane herniation and release of mtDNA.
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