Novel insights into the implication of KRIT1 in the maintenance of ROS homeostasis

KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral haemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. Recently, we found that KRIT1 is involved in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage (Goitre et al., 2010). Here, we report on updated studies that contribute to the unravelling of the KRIT1 role in the maintenance of homeostatic levels of ROS in cells, providing novel insights into the understanding of KRIT1 molecular and cellular functions, and raising the hypothesis that CCM pathogenesis may result from impaired endothelial cell defences against local oxidative stress events in sensitive cerebral microvascular districts carrying somatic or germline CCM mutations.