Figure 1. P66 Shc controls intracellular ROS metabolism at multiple sites. P66Shc (in blue) stimulates ROS production by plasma membrane oxidases through the association with membrane receptor and Rac activation of phagocitic oxidases. Upon phosphorylation and consequent Pin-1-mediated conformational changes, p66Shc (in red) translocates, through the TIM/TOM mitochondrial import machinery, within the mitochondrial inter-membrane space where it oxidizes reduced cytochrome c and catalyzes the partial reduction of O2 to H2O2. Then, p66Shc decreases the expression of ROS scavenging enzymes.