FUNDC1 inhibits NLRP3-mediated inflammation after intracerebral hemorrhage by promoting mitophagy in mice.

Inflammation is a fundamental element in secondary brain injury (SBI) besides intracerebral hemorrhage (ICH). Pyrin domain that contains 3 inflammasome (NLRP3) was regarded as a key role of the nod-like receptor family and played an important part in the inflammatory response following ICH-induced injury. FUN14 domain containing 1 (FUNDC1) is a kind of mitophagy receptor, which can eliminate mitochondrial dysfunction after hypoxia and mitochondrial stress. Previous research showed that mitophagy prevents inflammation through inhibiting NLRP3 inflammasome pathway. However, the relationship between FUNDC1 and ICH-induced inflammatory response stays uncertain. In this study, we investigate that FUNDC1 inhibit NLRP3 inflammasome activation by promoting mitophagy, thereby alleviate ICH-induced injury. We established ICH model by injecting tail venous blood into the basal ganglia of C57 mice (healthy, male adult). We injected siRNA to knockdown FUNDC1. In order to deeply seek for the mechanisms of FUNDC1 in ICH-induced injury, FUNDC1 was overexpressed by adeno-associated virus (AAV) and mitophagy was suppressed by specific inhibitor (mdivi-1). The protein level of FUNDC1 was upregulated and got peak at 12h after ICH. We noticed that silencing FUNDC1 can suppress mitophagy, promote NLRP3-mediated inflammation and exacerbate ICH injury. Furthermore, the results indicated that mitophagy participated in the inhibitory effect of FUNDC1 on NLRP3-mediated inflammatory response after ICH. Our results showed that FUNDC1 alleviated ICH-induced inflammation in mice by promoting mitophagy. Those data suggested that FUNDC1 may be a potential target for the treatment of ICH.