Mitochondrial play an essential role in apoptotic cell death. During apoptosis, mitochondrial outer membrane permeabilisation (MOMP) ensues, leading to caspase activation and rapid cell death. While apoptosis is immunosilent, under caspase inhibition MOMP drives an immunogenic form of cell death. We have previously found that this can be exploited to engage anti-tumour immunity thereby greatly enhancing cell-killing cancer therapies. Underpinning this immunogenicity, our previous work has revealed that permeabilised mitochondria activate pro-inflammatory NF-kB in dying tumour cells. Investigating its mechanistic basis, we have found that upon MOMP, mitochondria are extensively ubiquitinated leading to recruitment and activation the NF-kB adaptor molecular NEMO. I will discuss our ongoing work aimed at understanding how MOMP triggers ubiquitination leading to pro-inflammatory NF-kB signalling. Our overarching goal is to exploit this knowledge to enhance the anti-tumourigenic effects of cell-killing cancer therapy.