Study may improve survival of transplanted livers Leslie H. Lang  Gastroenterology  Volume 127, Issue 1, (July 2004) DOI: 10.1053/j.gastro.2004.05.055

Figure 1 The mitochondrial permeability transition (MPT) mediates both necrotic and apoptotic cell death after ischemia/reperfusion, death receptor ligation, toxic stresses, Ca2+ overloading, and reactive oxygen species (ROS) formation. NO protects against MPT-dependent cell killing by activating guanylyl cyclase (G-Cyclase), increasing cGMP, and subsequently stimulating protein kinase G (PKG). PKG-dependent phosphorylation inhibits the MPT and subsequent MPT-dependent cell death signaling pathways. When the MPT occurs severely, ATP depletion-dependent oncotic necrosis occurs due to plasma membrane failure, which is blocked by the cytoprotective amino acid, glycine. If ATP depletion is prevented by glycolysis of fructose, oncotic necrosis is inhibited. Instead, apoptosis occurs linked to MPT-dependent mitochondrial swelling, release of proapoptotic cytochrome c, and activation of caspases and endonucleases. Caspase activation requires ATP and is blocked by ATP depletion. If ATP depletion occurs after caspase activation, so-called secondary necrosis ensues. By blocking the MPT, CsA prevents both necrosis and apoptosis. The process involving shared pathways leading to both apoptosis and necrosis is termed necrapoptosis. Gastroenterology 2004 127, DOI: (10.1053/j.gastro.2004.05.055)