Figure 2.

Role of HO as master regulator of cell physiology. Highly active HO shifts the balance from heme mediated signaling towards HO product mediated signaling. Low activity results in an increased heme mediated signaling. Black arrows indicate direct processes associated with HO activity. Green arrows indicate elicited effects; red blocks indicate inhibitory actions of the indicated compounds. Interactions occurring in specialized cells, such as erythroid cells, or macrophages, are indicated by dotted lines. §, integrated stress response (ISR) pathway is activated via ATF4 by heme deficiency, indicating that physiological heme levels repress ATF4 activation. Abbreviations: ATF4, Activating transcription factor 4; BK_Ca, conductance Ca²⁺-activated K⁺ channels; BV/BR, biliverdin/bilirubin; cGMP, cyclic guanosine monophosphate, CO, carbon monoxide; COX, cytochrome c oxidase; DAMPs, danger associated molecular pattern; FLVCR, Feline leukemia virus subgroup C receptor; FPN1, ferroportin 1; PPP, pentose phosphates pathway; ROS, reactive oxygen species; TLR, Toll-like receptors.