Selective Mitochondrial Respiratory Complex I Subunit Deficiency Causes Tumor Immunogenicity

Targeting of specific metabolic pathways in tumor cells has the potential to sensitize them to immune-mediated attack. Previous studies had implicated mitochondria as a potential target for cancer therapies. We screen several complex I subunit deletions for their ability to induce an immune dependent anti-tumor response. Proteomic analysis of tumors lacking the complex I subunit NDUFS4 showed an increase in proteins involved in peptide antigen processing and presentation. We determined this increase in protein levels to be driven epigenetically through H3K27 acetylation from mitochondrial derived acetyl-CoA.