Sfxn5-flox Mouse

Sfxn5, a member of the sideroflexin family, is a metabolite transporter located in the mitochondrial membrane. Recombinant SFXN5 protein acts as a citrate transporter in vitro. It is involved in a citrate-cholesterol-PI(4,5)P2 pathway, which is crucial for neutrophil spreading, a key step in neutrophil adhesion, migration, and recruitment to inflammatory tissues. Sfxn5 also shows potential associations with metabolic regulation in brown adipose tissue and has been studied in relation to its expression in various tissues [1,2].

In neutrophil-related functional studies, Sfxn5 deficiency in neutrophils, achieved through small interfering RNA transfection or morpholino injection in mice and zebrafish respectively, significantly decreased neutrophil recruitment. It impaired neutrophil spreading and associated phenotypes like cell adhesion, chemotaxis, and ROS production. Actin polymerization, essential for neutrophil spreading, was partially inhibited by Sfxn5 deficiency. Mechanistically, Sfxn5-deficient neutrophils had decreased levels of cytosolic citrate, acetyl-CoA, cholesterol, and PI(4,5)P2. Exogenous supplementation with citrate or cholesterol could partially reverse these effects [1].

In conclusion, Sfxn5 plays a vital role in maintaining cytosolic citrate levels, ensuring sufficient cholesterol synthesis, and promoting actin polymerization in a PI(4,5)P2-dependent manner during neutrophil spreading, which is essential for neutrophil-mediated inflammatory responses. The gene knockout-like models in mice and zebrafish have provided key insights into Sfxn5's function in neutrophil-related processes, highlighting its potential significance in inflammatory-related disease areas [1].