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Updated: Jul 3, 2025

Author Spotlight: A Bicelle Crystallization Setup for ABC Transporter Membrane Proteins to Advance Drug Development
Published on: August 25, 2023
Roles of the ABCG2 Transporter in Protoporphyrin IX Distribution and Toxicity
Qian Qi1, Ruizhi Gu1, Junjie Zhu1
1Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (Q.Q., R.G., J.Z., X.M.) and Porphyria Laboratory and Center, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas (K.E.A.).
Abstract:
ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a membrane-bound transporter responsible for the efflux of various xenobiotics and endobiotics, including protoporphyrin IX (PPIX), an intermediate in the heme biosynthesis pathway. Certain genetic mutations and chemicals impair the conversion of PPIX to heme and/or increase PPIX production, leading to PPIX accumulation and toxicity. In mice, deficiency of ABCG2 protects against PPIX-mediated phototoxicity and hepatotoxicity by modulating PPIX distribution. In addition, in vitro studies revealed that ABCG2 inhibition increases the efficacy of PPIX-based photodynamic therapy by retaining PPIX inside target cells. In this review, we discuss the roles of ABCG2 in modulating the tissue distribution of PPIX, PPIX-mediated toxicity, and PPIX-based photodynamic therapy. SIGNIFICANCE STATEMENT: This review summarized the roles of ABCG2 in modulating PPIX distribution and highlighted the therapeutic potential of ABCG2 inhibitors for the management of PPIX-mediated toxicity.
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