MTDNA-DEPLETED U937 CELLS ARE SENSITIVE TO TNF AND FAS-MEDIATED CYTOTOXICITY

It has been proposed that TNF cytotoxicity is mediated by reactive oxy gen intermediates generated by uncoupling of mitochondrial respiration , We have compared sensitive U937 cells and derived cell lines deplete d of mtDNA for their ability to undergo TNF- and Fas-induced apoptosis , Cells lacking around 98% of mtDNA were still sensitive to TNF-induce d apoptosis, U937 cells devoid of mtDNA (U937-rho degrees) were resist ant to TNF, but this was due to the loss of its 55 kDa receptor, U937- rho degrees cells were also resistant to docosahexaenoic acid, which c auses U937 cell death by lipid peroxidation, These cells were sensitiv e to anti-Fas toxicity, The results indicate that TNF and Fas-induced toxicity occurs by a mechanism mostly independent of mitochondrial fre e radical generation.