Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death

摘要: Mitochondria play a critical role in mediating both apoptotic and necrotic cell death. The mitochondrial permeability transition (mPT) leads to swelling, outer membrane rupture the release of mediators. mPT pore is thought consist adenine nucleotide translocator, voltage-dependent anion channel, cyclophilin D (the Ppif gene product), prolyl isomerase located within matrix1,2. Here we generated mice lacking overexpressing heart. null are protected from ischaemia/reperfusion-induced death vivo, whereas D-overexpressing show swelling spontaneous isolated livers, hearts brains resistant vitro. Moreover, primary hepatocytes fibroblasts largely Ca2+-overload oxidative stress-induced However, Bcl-2 family member-induced does not depend on D, staurosporine or tumour-necrosis factor-α-induced Thus, required for Ca2+- damage-induced death, but member-regulated