[Retracted] Targeting Mitochondria as Therapeutic Strategy for Metabolic Disorders

Figure 1

Mitochondrial dysfunction regulates insulin signaling. Insulin interacts with α-subunits of its receptor (IR) on cell membrane. In response to stimuli, tyrosine residues undergo autophosphorylation, and the IR phosphorylates the insulin-receptor substrate-1 (IRS-1) in serine residues, activating Akt, with phosphorylation of the type 4 glucose transporter (GLUT4) to the cell membrane and facilitation of glucose uptake. Mitochondrial dysfunction inhibits insulin signaling, leading to insulin resistance, by (1) interfering with oxidation of fatty acyl-CoA and consequent accumulation of diacylglycerol, with consequent activation of protein kinase C and phosphorylation of IRS-1 in tyrosine residues preventing its activation, and (2) through the generation of ROS, which inhibits IRS phosphorylation in serine residues.