Genetic control of necrosis—another type of programmed cell death

Necrosis has been thought to be an accidental or uncontrolled type of cell death rather than programmed. Recent studies from diverse organisms show that necrosis follows a stereotypical series of cellular and molecular events: swelling of organelles, increases in reactive oxygen species and cytoplasmic calcium, a decrease in ATP, activation of calpain and cathepsin proteases, and finally rupture of organelles and plasma membrane. Genetic and chemical manipulations demonstrate that necrosis can be inhibited, indicating that necrosis can indeed be controlled and follows a specific ‘program.’ This review highlights recent findings from C. elegans, yeast, Dictyostelium, Drosophila, and mammals that collectively provide evidence for conserved mechanisms of necrosis.