The hypoxic preconditioning agent deferoxamine induces poly(ADP-ribose) polymerase-1-dependent inhibition of the mitochondrial respiratory chain

We previously reported that treatment with a single dose of deferoxamine (DFO), which acts as a hypoxic-mimetic agent, only induces reactive oxygen species (ROS) production in the presence of poly(ADP-ribose) polymerase (PARP-1). Given that mitochondria are one of the main sources of ROS, the present study was designed to assess the effect of DFO treatment on the activity of mitochondrial respiratory chain complexes, and more importantly, to determine whether this effect is modulated by PARP-1. We found that DFO treatment induced a progressive decline in complex II and IV activity, but that this activity was preserved in PARP-1 knock-out cells, demonstrating that this decrease is mediated by PARP-1. We also confirmed that complex II inhibition after DFO treatment occurs in parallel with poly-ADP ribosylation. Consequently, we recommend that PARP-1 activation be taken into account when using DFO as a hypoxia-mimetic agent, because it mediates alteration of the mitochondrial respiratory chain.