 In solid-organ transplantation, ischemia-reperfusion injury can occur when blood returns to tissue for the first time in the transplant recipient.A major contributor to tissue damage results from activation of regulated necroptosis, which could include contributions from both necroptosis and mitochondrial permeability transition.Treatment with the drug cyclosporine, which represses the mitochondrial permeability transition effector Cyclophilin D, improves tissue survival primarily by inhibiting necrotic cell death, rather than its additional function as an immunosuppressant.