Characterization of TNF-induced caspase-independent necroptosis

Caspase-independent programmed necrotic cell death (necroptosis) has recently been described. Previously described models of necroptosis required 16 h or more of induction, which made the interpretation of findings somewhat difficult. In human monocytic leukemia cell line U937 necroptosis could be induced within 6 h by combination of TNF and Z-VAD-fmk. Here we show that the reduction in intracellular ATP levels may not be the sole determinant of necroptosis, and that necroptosis is associated with the loss of mitochondrial membrane potential, but not the activation of Bak/Bax or calcineurin.