Research Paper Volume 12, Issue 24 pp 25035—25059

Figure 8. Schematic mechanisms underlying DOR mediated protection against mitochondrial injury under hypoxic and/or MPP⁺ insults. Solid green arrow: strong mitoprotection. Dotted green arrow: weak mitoprotection. Green flat arrow: strong inhibition. Note that although DOR activation up-regulated PINK1 in both conditions of MPP⁺ and hypoxia, DOR exhibited a more powerful mitoprotective capacity against MPP⁺ insults through stabilizing mitochondrial potential, restoring mitochondrial function, and inhibiting anti-cytochrome c release from mitochondria to cytosol. Moreover, DOR activation differentially regulated ROS under MPP⁺ vs. hypoxia, and it also specifically promoted the recruitment of Parkin in the mitochondria, thus enhanced the mitophagy in a PINK1-Parkin dependent manner in MPP⁺ conditions but not in hypoxia.