CNR - Institute of Neuroscience CNR
Institute of Neuroscience
 

Project

The mitochondrial permeability transition (MPT)

Loss of the characteristic impermeability of the inner membrane through the MPT causes cell death in pharmacological (chemotherapy, environmental poisons) and pathological (ischemia/reperfusion (I/R)) settings. MPT-inducing and -repressing factors and conditions, in vivo occurrence and regulation, the proteins involved, and the pathophysiological consequences of the phenomenon are all active topics of research at Padova.

 

Recent progress. The molecular composition of the MPT Pore is still unknown, but the genetic ablation of the mitochondrial cyclophilin (CyPD) has shown that this protein, although dispensable for the formation of a Ca-sensitive PTP, is and important regulator. Experiments with mitochondria isolated from CyPD KO mice (Ppif-/-) have shown that inorganic phosphate (Pi) is specifically required for MPTP desensitization by Cyclosporin A (CsA) or by genetic inactivation of CyPD.

 

The MPT involvement in pathopysiology is studied in particular in the context of myocardial ischemia and heart failure, in hepatotoxicity and in connection with some forms of muscular dystrophy. Through a chain of signalling events under investigation, the lack of an extracellular matrix component impacts on mitochondrial and cellular functionality. This discovery is opening interesting therapeutic perspectives, currently based on the use of non-immunosuppressive analogues of cyclosporine A, the paradigmatic inhibitor of the MPT. The same drugs may well develop into useful tools to limit I/R damage.

Publications

  • Basso E, Petronilli V, Forte MA, Bernardi P (2008) Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation. J. Biol. Chem. 283:26307-11.
  • Basso E, Fante L, Fowlkes J, Petronilli V, Forte MA, Bernardi P (2005) Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D. J. Biol. Chem. 280:18558-61.

 

PI photo

Paolo Bernardi

Contact information

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Participating staff
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