Figure 7. Clusterin (CLU) gene products are proposed to be major players in defence and initiation responses to trauma that directly influence multiple organ dysfunction (MOD). CLU gene activation is a molecular switch between life and death. At low doses, secretory clusterin (sCLU) production provides a cytoprotective molecular chaperone defence mechanism in clearing cell debris from traumatised tissue. At higher doses, the pre-nuclear form of CLU (pnCLU, a form of the protein that resides dormant in the cytoplasm of most cells) becomes activated through an as yet uncharacterised post-translational mechanism. Activated nuclear clusterin (nCLU), a pro-death mature 55 kDa protein that causes apoptosis, is formed. Widespread activation of nCLU in organs after MOD-causing traumatic insults then facilitates multiple organ failure. See text for further discussion. ROS, reactive oxygen species.