Figure 8

Proposed mechanisms of atypical RIP1-dependent cell death by ESA. (1) ESA activates phosphatases such as calcineurin, resulting in dephosphorylation of RIP1. (2) Phosphorylated MEK1/2/ activates ERK1/2 associated with RIP1. (3) AIF dephophosrylation occurs. (4) Localization of AIF and ERK1/2 in the nucleus initiates the cell death accompanied by ROS generation in mitochondria. Toc blocks the final stage of ROS production effectively, by which cells can survive.