Fig. 10.

Potential roles for the UPS and 11S-activated proteasome in short- and long-duration ischemia. In the nonischemic heart, oxidized, misfolded, and ubiquitinated proteins are degraded through both ubiquitin- and nonubiquitin-mediated pathways, recycling the constituent amino acids, and maintaining a dynamic balance between pro-survival and pro-death signals. During an ischemic insult resulting in cell death or dysfunction, UPS function is inhibited leading to accumulation of oxidized and ubiquitinated proteins. In addition, a condition known as dysregulation may occur in which normal UPS-mediated degradation of pro-death proteins is depressed. Reproduced with permission from Oxford University Press.²¹⁴