Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 155 Volker Hall, 1720 2nd Ave S., Birmingham, AL, 35294-0019, USA.
Sci Rep. 2022 Jan 31;12(1):1625. doi: 10.1038/s41598-022-05582-4.
Sulfotransferase 4A1 (SULT4A1) is an orphan member of the cytosolic SULT superfamily that contains enzymes that catalyze the sulfonation of hydrophobic drugs and hormones. SULT4A1 has been assessed through all classical SULT approaches yet no SULT activity has been reported. To ascertain SULT4A1 function and activity, we utilized Saccharomyces cerevisiae as a model system, which exhibits no endogenous SULT activity nor possesses SULT-related genes. We observed that ectopic SULT4A1 expression in yeast displays similar subcellular localization as reported in mouse neurons and observed that SULT4A1 is associated with the outer mitochondria membrane. SULT4A1 expression stimulates colony formation and protects these cells from hydrogen peroxide and metabolism-associated oxidative stress. These SULT4A1-mediated phenotypes are dependent on extracellular sulfate that is converted in yeast to PAPS, the universal sulfonate donor for SULT activity. Thus, heterologous SULT4A1 expression in yeast is correctly distributed and functional, and SULT4A1 antioxidant activity is sulfate dependent supporting the concept that SULT4A1 has sulfate-associated activity.
磺基转移酶 4A1（SULT4A1）是细胞溶质 SULT 超家族的孤儿成员，其中包含催化疏水性药物和激素磺化的酶。已经通过所有经典的 SULT 方法评估了 SULT4A1，但尚未报道其 SULT 活性。为了确定 SULT4A1 的功能和活性，我们利用酿酒酵母作为模型系统，该系统没有内源性 SULT 活性，也不具有 SULT 相关基因。我们观察到，酵母中外源 SULT4A1 的表达显示出与在小鼠神经元中报道的相似的亚细胞定位，并且观察到 SULT4A1 与外线粒体膜相关联。SULT4A1 的表达刺激集落形成，并保护这些细胞免受过氧化氢和与代谢相关的氧化应激。这些 SULT4A1 介导的表型依赖于细胞外硫酸盐，该硫酸盐在酵母中转化为 PAPS，即 SULT 活性的通用磺酸盐供体。因此，酵母中异源 SULT4A1 的表达是正确分布和功能的，并且 SULT4A1 的抗氧化活性依赖于硫酸盐，支持 SULT4A1 具有硫酸盐相关活性的概念。
