Proteasomes modulate balance among proapoptotic and antiapoptotic Bcl-2 family members and compromise functioning of the electron transport chain in leukemic cells

The mechanism underlying apoptosis induced by proteasome inhibition in leuk emic Jurkat and Namalwa cells was investigated in this study. The proteasom e inhibitor lactacystin differentially regulated the protein levels of proa poptotic Bcl-2 family members and Bik was accumulated at the mitochondria, Bik overexpression sufficed to induce apoptosis in these cells. Detailed ex amination along the respiration chain show ed that lactacystin compromised a step after complex III, and exogenous cytochrome c could overcome this co mpromise, probably as a result, the succinate-stimulated generation of mito chondrial membrane potential was significantly diminished. Bcl-x(L), intera cted with Bik in the cells, and Bcl-x(L) overexpression prevented cytochrom e c leakage out of the mitochondria, corrected the mitochondrial membrane p otential defect, and protected the cells from apoptosis, These results show that proteasomes can modulate apoptosis of lymphocytes by affecting the ha lf-life of Bcl-2 family members, Bik being one of them.