NADH Dehydrogenase Ubiquinone Fe-S Protein 3 (NDUFS3)

NDUFS3 cleavage generated reactive oxygen species, disrupted the mitochondrial membrane potential, and interfered with NADH oxidation and ATP synthesis. The generation of reactive oxygen species induced translocation of the SET complex from the cytosol to the nucleus, followed by GZMA-mediated activation of the SET complex DNases NM23H1 (NME1) and TREX1, leading to DNA damage and cell death. SET complex translocation, DNase activation, and cell death were blocked by superoxide scavengers or by overexpression of a cleavage-resistant NDUFS3 mutant. The predicted 264-amino acid human NDUFS3 protein shares 90% identity with the bovine protein. The first 36 amino acids of human NDUFS3 comprise a possible mitochondrial targeting sequence.