Fig. 9

A potential mechanism of the dual roles of HMOX1 in neural retinas. Low-levels of HMOX1 reduce oxidative stress by catalyzing the degradation of heme to biliverdin, CO and ferrous iron because of the consumption of molecular oxygen in the heme oxygenase reaction. Although ferrous iron leads to mild ER stress, the adaptive UPR likely restores ER homeostasis. In contrast, high-levels of HMOX1 induce intense ER stress via iron-overload, resulting in protein unfolding or misfolding in the dysfunctional ER, which in turn leads to mislocalization of rhodopsin in photoreceptor cells. The intense ER stress, rather than inducing an adaptive UPR, triggers a proapoptotic UPR that leads to cell death via the stimulation of the DDIT3 pathway. Thus, the level of ferrous iron might represent the switching point determining whether HMOX1 plays a protective or a deleterious role in neural retinas