Changes of cellular redox homeostasis and protein folding in diabetes

Ch ha an ng ge es s o of f c ce el ll lu ul la ar r r re ed do ox x h ho om me eo os st ta as si is s a an nd d p pr ro ot te ei in n f fo ol ld di in ng g i in n d di ia ab be et te es s Chaperones are conserved and abundant proteins of the cell. They not only help to fold the newly synthesized proteins to get their final structure, but are also involved in many other events of the cellular life, such as signal transduction or protein degradation. A subset of chaperones takes part in the the formation of disulfide bonds, ion pairs and in the prolin cis-trans isomerisation of folding proteins. Disulfide bond formation is necessary for the active, functioning state of most secreted or plasma membrane proteins. Chaperones involved in disulfide bond formation need a highly regulated redox environment, which is provided by the lumen of the endoplasmic reticulum. The redox balance is maintained by many enzymatic systems, as well as by a permanent supply of coenzymes taking part in the electron transport chain. Diabetes is a well known metabolic disease, where one of the general symptoms is the presence of extensive oxidative stress. Here we give an overview of the role of oxidative homeostasis and chaperones in protein folding and summarize our current knowledge on changes of both redox balance and chaperone function in diabetes.