Molecular Views into the Synthesis and Activation of Flavocytochrome b558 in Phagocytic Cells—Focus on the Role of EROS

Recent advances in the structural characterization of the phagocyte NADPH oxidase coupled with the description of its chaperone EROS for Essential for Reactive Oxygen Species have led to a better understanding of its function and activation in phagocytic cells. This review examines the role of EROS chaperone in flavocytochrome b558 biosynthesis and function and in physiological and pathological conditions. Based on experimental data and structural insights, we synthesize knowledge from former work on flavocytochrome b558 synthesis and structure combined with recent advances on the specific role of EROS chaperone on the potential control of Reactive Oxygen Species (ROS) production by c flavocytochrome b558. We particularly emphasize its role in the pathological context of Chronic Granulomatous Disease (CGD), with already described EROS mutations (known as CGD5), as well as rare X91minus-CGD (or X91−-CGD) cases characterized by low flavocytochrome b558 expression in phagocytes that could be due to a lack of interaction with EROS. Future works should address in more detail how EROS binding and release from flavocytochrome b558 is regulated, and whether the inhibitory effect on ROS production that was observed in EROS overexpression studies is relevant in a more physiological context.