PRKN and Parkinson disease: As reported for other proteins [1, 41–46], we speculate that when SIAH2 is activated during hypoxia, it translocates to depolarized mitochondria where it induces the degradation of NCX3 and AKAP121 via the proteasome, similar to the behavior of other protein complexes including the Pink1/parkin complex in Parkinson’s disease [46–48].