Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

Figure 1

The figure illustrates the role of UCP regulation on cell death or survival. H₂O₂, generated from the dismutation of superoxide anion () in both sides of mitochondrial inner membrane (MIM), oxidizes cardiolipin (CL) to produce oxidized CL (oxCL). This reaction is orchestrated with cytochrome c (cyt c) dissociation from MIM. Then free cyt c in IMS (intermembrane space) can cross the MOM (mitochondria outer membrane) by a pore formed by BAX and BAK and induced by oxidized cardiolipin (oxCL). When UCPs are activated, a proton leak (through UCPs) induces a mild uncoupling reducing the formation of and H₂O₂ and in turn cyt c release and apoptosis. In addition, cells with deleted UCP or treated with UCP inhibitors such as chromanes or genipin favor ROS generation, cyt c release, cell death, and heart failure.