nucleotide excision repair mitochondria briefs

Mitoferrin-2 (SLC25A28) is synthetic lethal with nucleotide excision repair loss

Yang, Hoeg, Durocher, Mouw, Offit, Lipkin and colleagues rank SLC25A28 as the top CRISPR hit that kills ERCC4-null bladder-cancer cells while sparing isogenic NER-proficient cells. SLC25A28 is mitoferrin-2, the mitochondrial inner-membrane carrier that imports ferrous iron for heme and iron-sulfur cofactor assembly. Loss of the carrier raises intracellular reactive oxygen species and DNA-damage signatures, which NER-deficient cells cannot clear. The authors do not report a named Fe-S nuclearity. The metal site in play is the mitochondrial Fe2+ import step, not a counted [2Fe-2S] or [4Fe-4S] enzyme.