Kawaguchi Takahiro, Ishibashi Yohei, Matsuzaki Momoko, Yamagata Satomi, Tani Motohiro
Department of Chemistry, Faculty of Sciences, Kyushu University, 744, Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 744, Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Biochem Biophys Rep. 2024 Jul 13;39:101785. doi: 10.1016/j.bbrep.2024.101785. eCollection 2024 Sep.
Myriocin is an inhibitor of serine palmitoyltransferase involved in the initial biosynthetic step for sphingolipids, and causes potent growth inhibition in eukaryotic cells. In budding yeast, Rsb1, Rta1, Pug1, and Ylr046c are known as the Lipid-Translocating Exporter (LTE) family and believed to contribute to export of various cytotoxic lipophilic compounds. It was reported that Rsb1 is a transporter responsible for export of intracellularly accumulated long-chain bases, which alleviate the cytotoxicity. In this study, it was found that LTE family genes are involved in determination of myriocin sensitivity in yeast. Analyses of effects of deletion and overexpression of LTE family genes suggested that all LTEs contribute to suppression of cytotoxicity of myriocin. It was confirmed that overexpression suppressed reduction in complex sphingolipid levels caused by myriocin treatment, possibly exporting myriocin to outside of the cell. These results suggested that LTE family genes function as a defense mechanism against myriocin.
嗜热栖热放线菌素是一种参与鞘脂生物合成初始步骤的丝氨酸棕榈酰转移酶抑制剂，可在真核细胞中引起强烈的生长抑制。在芽殖酵母中，Rsb1、Rta1、Pug1和Ylr046c被认为是脂质转运外排蛋白（LTE）家族，并且被认为有助于各种细胞毒性亲脂性化合物的外排。据报道，Rsb1是一种负责将细胞内积累的长链碱基外排的转运蛋白，可减轻细胞毒性。在本研究中，发现LTE家族基因参与酵母中嗜热栖热放线菌素敏感性的测定。对LTE家族基因缺失和过表达效应的分析表明，所有LTE都有助于抑制嗜热栖热放线菌素的细胞毒性。证实过表达抑制了嗜热栖热放线菌素处理引起的复合鞘脂水平的降低，可能是将嗜热栖热放线菌素转运到细胞外。这些结果表明，LTE家族基因作为一种针对嗜热栖热放线菌素的防御机制发挥作用。
