Mitochondrial H<sub>2</sub>O<sub>2</sub> as an enable signal for triggering autophosphorylation of insulin receptor in neurons

Abstract

In this study, we demonstrated for the first time that the receptor autophosphorylation occurs only if mitochondrial H2O2 signal exceeds a certain threshold. This finding provides novel insights into the mechanisms underlying neuronal response to insulin. The neuronal insulin receptor is activated if two conditions are met: 1) insulin binds to the receptor, and 2) the H2O2 signal surpasses a certain threshold, thus, enabling receptor autophosphorylation in all-or-nothing manner. Although the physiological rationale for this control remains to be determined, we propose that malfunction of mitochondrial H2O2 signaling may lead to the development of cerebral insulin resistance.