ABCG2, also known as breast cancer resistance protein (BCRP), is an ABC transporter. It functions as a poly-specific efflux pump, transporting a broad spectrum of substrates such as xenobiotics, drugs, and nutrients out of cells. This is crucial in protecting organisms from harmful substances, regulating oral bioavailability, and forming barriers like the blood-brain, blood-testis, and maternal-fetal barriers [2,3]. Genetic models, like KO mouse models, are valuable for studying ABCG2's functions.

In macrophages, ABCG2 exports itaconate from the cytosol to the extracellular space in an ATPase-dependent manner. Macrophages deficient in ABCG2-mediated itaconate export show elevated transcription factor TFEB-dependent lysosomal biogenesis and antibacterial innate immunity. In a mouse model of S. typhimurium infection, this deficiency also promotes antibacterial innate immune defense, indicating that ABCG2-mediated itaconate export limits TFEB-dependent lysosomal biogenesis and antibacterial innate immunity in inflammatory macrophages [1].

In conclusion, ABCG2 is an important efflux transporter with roles in protecting the body from xenobiotics and in drug pharmacokinetics. The study of ABCG2-deficient mouse models has revealed its role in regulating antibacterial innate immunity in macrophages, which may have implications for treating human bacterial infections.

References:

1. Chen, Chao, Zhang, Zhenxing, Liu, Caiyun, Liu, Ping, Li, Xinjian. 2024. ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis. In Cell metabolism, 36, 498-510.e11. doi:10.1016/j.cmet.2023.12.015. https://pubmed.ncbi.nlm.nih.gov/38181789/

2. Safar, Zsolt, Kis, Emese, Erdo, Franciska, Zolnerciks, Joseph K, Krajcsi, Peter. 2019. ABCG2/BCRP: variants, transporter interaction profile of substrates and inhibitors. In Expert opinion on drug metabolism & toxicology, 15, 313-328. doi:10.1080/17425255.2019.1591373. https://pubmed.ncbi.nlm.nih.gov/30856014/

3. Robey, Robert W, To, Kenneth K K, Polgar, Orsolya, Dean, Michael, Bates, Susan E. 2008. ABCG2: a perspective. In Advanced drug delivery reviews, 61, 3-13. doi:10.1016/j.addr.2008.11.003. https://pubmed.ncbi.nlm.nih.gov/19135109/