To elucidate which aspects of mitochondrial dysfunction trigger Rnf213 transcriptional induction, we tested four alternative hypotheses in mouse embryonal fibroblasts (MEF), human umbilical vein endothelial cells (HUVEC), or human neuroblastoma cells (SH-SY5Y):Dysfunctional mitochondria become cytotoxic via mitochondrial precursor overaccumulation stress (mPOS) [40]. Here, RNF213 is linked to neuroblastoma.