Colson Cecilia, Wang Yujue, Atherton James, Su Xiaoyang
Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
bioRxiv. 2024 Jul 24:2024.07.23.604788. doi: 10.1101/2024.07.23.604788.
Solute carriers (SLC) are membrane proteins that facilitate the transportation of ions and metabolites across either the plasma membrane or the membrane of intracellular organelles. With more than 450 human genes annotated as SLCs, many of them are still orphan transporters without known biochemical functions. We developed a metabolomic-transcriptomic association analysis, and we found that the expression of SLC45A4 has a strong positive correlation with the cellular level of γ-aminobutyric acid (GABA). Using mass spectrometry and the stable isotope tracing approach, we demonstrated that SLC45A4 promotes GABA synthesis through the Arginine/Ornithine/Putrescine (AOP) pathway. SLC45A4 functions as a putrescine transporter localized to the mitochondrial membrane to facilitate GABA production. Taken together, our results revealed a new biochemical mechanism where SLC45A4 controls GABA production.
溶质载体（SLC）是一类膜蛋白，可促进离子和代谢物跨质膜或细胞内细胞器膜的运输。超过450个人类基因被注释为SLC，其中许多仍是功能未知的孤儿转运蛋白。我们开展了一项代谢组学-转录组学关联分析，发现SLC45A4的表达与γ-氨基丁酸（GABA）的细胞水平呈强正相关。使用质谱和稳定同位素示踪方法，我们证明SLC45A4通过精氨酸/鸟氨酸/腐胺（AOP）途径促进GABA合成。SLC45A4作为一种定位在线粒体膜上的腐胺转运蛋白，促进GABA的产生。综上所述，我们的结果揭示了一种新的生化机制，即SLC45A4控制GABA的产生。
