(36) THE RELATIONSHIP BETWEEN THE MITOCHONDRIAL PERMEABILITY TRANSITION AND CELL DEATH

V. Petronilli^1,2, D. Penzo², L. Scorrano², P. Bernardi^1,2 and F. Di Lisa^1,3
1CNR Unit for the Study of Biomembranes
²Department of Biomedical Sciences 
³Department of Biological Chemistry, Viale Giuseppe Colombo 3, I-35121 Padova, Italy

We have investigated the relationship between opening of the permeability transition pore (PTP), mitochondrial depolarization, cytochrome c release and occurrence and mode of cell death in rat hepatoma MH1C1 cells. Treatment with A23187 or arachidonic acid induces PTP opening in situ with similar kinetics, as assessed by the calcein loading-Co²⁺ quenching technique [1]. Yet, depolarization is rapid and extensive with arachidonic acid and slow and partial with A23187. Cyclosporin A-inhibitable release of cytochrome c and cell death correlate with mitochondrial depolarization rather than with PTP opening as such. Cells are apoptotic at early time points but switch to necrosis at longer incubation times, a likely consequence of ATP depletion. We conclude that short PTP openings may have little impact on cell viability, while longer openings cause release of cytochrome c and result in cell death. Modulation of the open time appears to be the key element in determining the outcome of stimuli that impinge on the PTP.

[1]  Petronilli, V. et al. (1999) Biophys. J. 76:725-734

© 1999 Wadsworth Center, All Rights Reserved. Legal & Privacy Notices