Oxidation products of polyamines induce mitochondrial uncoupling and cytochrome c release.

Spermine is shown to uncouple isolated mitochondria and to trigger the selective release of cytochrome c. Pargyline, an inhibitor of amine oxidase (AO), fully prevented these effects of spermine, which instead were potentiated by exogenous AO. Hydrogen peroxide, an oxidation product of spermine, mimicked the effects of spermine on mitochondria, while the addition of catalase prevented them. Spermidine and putrescine also caused mitochondrial uncoupling and triggered cytochrome c release, with a potency which correlated with the substrate preference of mitochondrial AO. Pargyline protected human lymphoma U937 cells against UVB-induced apoptosis, by reducing AO activity, mitochondrial uncoupling and cytochrome c release.