Fundc1-flox Mouse

FUNDC1, also known as FUN14 domain containing 1, is an integral mitochondrial outer-membrane protein. It plays a critical role in regulating mitochondrial quality control (MQC) through mitophagy. FUNDC1 can interact with various proteins, participating in multiple pathways such as the regulation of mitochondrial dynamics, and is associated with numerous biological processes and diseases [4,5]. Genetic models, like knockout (KO) mice, have been crucial in studying its functions.

In liver fibrosis, FUNDC1 deletion protected against CCl4-induced hepatic anomalies and ferroptosis in mice. Mechanically, FUNDC1 interacted with GPx4 to facilitate its mitochondrial translocation and degradation by mitophagy, triggering ferroptosis [1]. In doxorubicin-induced cardiotoxicity, FUNDC1 deficiency aggravated cardiac dysfunction and cardiomyocyte PANoptosis. FUNDC1 countered cytoplasmic release of mitochondrial DNA and activation of PANoptosome through interaction with TUFM [2]. In hypoxic pulmonary hypertension, Fundc1 KO mice were more resistant to the disease, while Fundc1 transgenic mice developed severe hemodynamics changes and pulmonary vascular remodeling. FUNDC1-mediated mitophagy activated the ROS-HIF1α pathway and promoted pulmonary artery smooth muscle cell proliferation [3].

In conclusion, FUNDC1 is essential for mitochondrial quality control through mitophagy. Studies using KO/CKO mouse models have revealed its roles in various disease conditions, including liver fibrosis, cardiotoxicity, and pulmonary hypertension. Understanding FUNDC1 functions provides potential therapeutic targets for these diseases.