Uncoupling protein UCP2: When mitochondrial activity meets immunity

Abstract 

Uncoupling protein 2 (UCP2) belongs to the family of mitochondrial carriers. Here, we highlight recent findings regarding UCP2 function in the immune system. UCP2 controls immune cell activation by modulating MAPK pathways and the production of mitochondrial reactive oxygen species. In several models of infection, inflammation and autoimmunity, a regulatory impact of UCP2 was demonstrated by its direct implication in the production of cytokines and nitric oxide and in cell migration. In addition, UCP2 is reported as a key protein for oxidation of fatty acids, glutamine and glucose. Therefore we present a model of how the regulation of nutrient oxidation by UCP2 promotes immune cell activation.

Abbreviations: EAE, experimental autoimmune encephalomyelitis, IFN, interferon, IL, interleukin, iNOS, inducible nitric oxide synthase, IP10, IFN-inducible protein 10, KO, knock out, LPS, lipopolysaccharide, MCP1, monocyte chemotactic protein-1, MOG, myelin oligodendrocyte glycoprotein, MIG, monokine induced by IFN-γ, NO, nitric oxide, PGC, peroxisome proliferator-activated receptor-gamma coactivator, ROS, reactive oxygen species, TLR, Toll-like receptor, TNF, tumor necrosis factor, UCP, uncoupling protein, WT, Wild-type

Keywords: Mitochondria, Uncoupling protein 2, Reactive oxygen species, Inflammation, Immune response