Figure 2.

Molecular mechanism underlying oxygen-sensing in TRPA1 channel. In hypoxia, a decrease in O₂ concentrations relieves TRPA1 from the prolyl hydroxylation, which activates TRPA1. The relief can be achieved by insertion of unmodified TRPA1 proteins to the plasma membrane and internalization of hydroxylated TRPA1 proteins. In hyperoxia, O₂ oxidizes Cys633, Cys856 or both, thereby activating TRPA1. TRPA1 may at least take two oxidized state upon hyperoxia: a reversibly oxidized state (State 1) and a relatively stable oxidized state (State 2). Oxidized TRPA1 proteins can be also internalized. Modified from Takahashi et al.⁹⁰⁾