mitochondrial permeability transition

Opening of high conductance permeability transition pores in mitochondria initiates onset of the mitochondrial permeability transition (MPT).

The MPT is a causative event, leading to necrosis and apoptosis in hepatocytes after oxidative stress, Ca(2+) toxicity, and ischemia/reperfusion.

CsA blocks opening of permeability transition pores and protects cell death after these stresses. In contrast to necrotic cell death which is a consequence of ATP depletion, ATP is required for the development of apoptosis.

Reperfusion and the return of normal pH after ischemia initiate the MPT, but the balance between ATP depletion after the MPT and ATP generation by glycolysis determines whether the fate of cells will be apoptotic or necrotic death.

Thus, the MPT is a common pathway leading to both necrotic and apoptotic cell death after ischemia/reperfusion.

References

 Kim JS, He L, Qian T, Lemasters JJ. Role of the mitochondrial permeability transition in apoptotic and necrotic death after ischemia/reperfusion injury to hepatocytes. Curr Mol Med. 2003 Sep;3(6):527-35. PMID: 14527084

 Kim JS, He L, Lemasters JJ: Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 304:463, 2003. PMID: 12729580