Fig. 9: Summary of ATMs mitochondria-targeting IR-61.

IR-61 selectively targets ATMs via the endocytosis pathway and preferentially accumulates in the mitochondria. IR-61 induces transiently increased mitochondrial ROS and promotes phosphorylation of Akt and Acly, which further potentiates mitochondrial oxidative phosphorylation by increasing the content and activity of the mitochondrial complexes to inhibit pro-inflammatory macrophage (M1) activation, and improve obesity and associated disorders, such as insulin resistance and hepatic steatosis.