BCL-2 BLOCKS LOSS OF MITOCHONDRIAL-MEMBRANE POTENTIAL WHILE ICE INHIBITORS ACT AT A DIFFERENT STEP DURING INHIBITION OF DEATH INDUCED BY RESPIRATORY-CHAIN INHIBITORS

Bcl-2, Bcl-x(L), CrmA and tetrapeptide ICE inhibitor reduce the extent of necrotic cell death induced by cyanide, which primarily damages mi tochondria, Although none of them affects the drastic decrease in ATP levels induced by cyanide, Bcl-2 and Bcl-x(L) but not CrmA or ICE inhi bitor inhibit the cyanide-induced decrease in mitochondrial membrane p otential, A similar blocking effect is observed on necrotic cell death induced by other respiration inhibitors, rotenone and antimycin A, an d on apoptotic cell death induced by etoposide or calcium ionophore. T hese results indicate that Bcl-2 and Bcl-x(L) protect mitochondria aga inst the loss of function during both apoptosis and at least some form s of necrotic cell death, The ICE family proteases act at a different step other than the loss of mitochondrial membrane potential.