Arginine for mitochondrial oxidative enzymopathy

Abstract

Although mitochondria are known to be a major source of reactive oxygen species (ROS), and oxidative stress is thought to contribute to pathology in sickle cell disease, in this issue of Blood, Morris et al have shown that arginine therapy can improve mitochondrial function and decrease oxidative stress.

Mitochondrial therapeutics. Red cell hemolysis produces cell-free hemoglobin and heme, which leads to NO scavenging, formation of ROS, and platelet activation. Red cells also release ADP, which activates platelets and arginase, decreasing NO bioavailability (not shown). Hemoglobin leads to decreased platelet mitochondrial complex V activity and oxidative stress. Arginine therapy improves mitochondrial function in sickle cell patients, but whether the mechanism involves direct inhibition of platelet activation by NO, countering the deleterious effects of hemoglobin/heme, transiently modulating platelet complex I, or by  limiting systemic-ischemia-reperfusion stress remains to be determined. Professional illustration by Patrick Lane, ScEYEnce Studios.