Induction of the mitochondrial permeability transition by peroxynitrite

The mitochondrial respiratory chain is a major source of superoxide within cells. This superoxide reacts with nitric oxide to form the damaging oxidant peroxynitrite which may be a significant contributor to mitochondrial oxidative damage. One aspect of this mitochondrial oxidative damage is the induction of the mitochondrial permeability transition, caused by opening a pore in the mitochondrial inner membrane. We found that peroxynitrite was an effective inducer of the mitochondrial permeability transition. In addition, simultaneous generation of nitric oxide and superoxide, mimicking the formation of peroxynitrite in vivo, also induced the mitochondrial permeability transition. Therefore peroxynitrite may damage cells through its induction of the mitochondrial permeability transition. Recently we have focussed on two related questions: how peroxynitrite oxidation of protein thiols and nicotinamide nucleotides induces the permeability transition and on pathways by which the permeability transition may lead to apoptosis within intact cells.