The P5 disulfide switch: taming the aging unfolded protein response.

Aging cells are characterized by a loss of proteostasis and a decreased ability to survive under environmental stress. Regulation of the UPR in aging cells has been under much scrutiny, and studies have shown that the UPR in these cells differs considerably from younger cells with regard to the induction of apoptosis and chaperone activity. The role of IRE-1 and PERK in UPR-associated apoptosis makes the regulation of these signaling cascades an important target of study. The seemingly contradictory findings regarding the role of P5 in activating and deactivating these responses warrant further investigation and may hold the key to unlocking the role of this protein in various pathological conditions. Another important target for study with regard to P5 is the effects of the localization of this protein in the mitochondria and the consequences, if any, of these effects on the activation of the UPR.