Figure 1. Intracellular iron regulation and ROS generation.

Ferric iron [Fe(III), Fe³⁺] is bound with transferrin (Tf) and transported via TfR1 (Transferrin receptor 1), and ferrous iron [Fe(II), Fe²⁺] enters the cells mostly through several transport systems, such as divalent metal transporter (DMT1) and L-type voltage-dependent Ca²⁺ channels (LTCC) [90]. Intracellular Fe(H) moves to mitochondria and generates ROS via the Fenton reaction (1). Fe(III) and Fe(II) also mediate membrane lipid peroxidation by catalyzing the reductive cleavage of hydroperoxysides (ROOH) resulting in the formation of alkoxyl (RO) and peroxyl (RO₂) radicals (2). The red lightning bolts indicate free radical oxidative damage and propagation of free radicals.