美国威斯康星大学麦迪逊分校David J. Pagliarini小组发现，真菌线粒体IPP转运需要Hem25p。相关论文于2023年10月9日在线发表于国际学术期刊《自然—细胞生物学》杂志上。

研究人员通过基因筛选、代谢追踪和靶向摄取测定相结合的方法，揭示了Hem25p，即血红素生物合成所需的线粒体甘氨酸转运体，在酿酒酵母中兼作焦磷酸异戊烯酯（IPP）转运体。缺乏Hem25p的线粒体不能有效地将IPP结合到早期辅酶 Q（CoQ，泛醌）前体中，导致CoQ损失和CoQ生物合成蛋白的周转。在大肠杆菌中表达Hem25p能使其强有力地吸收IPP并将其纳入CoQ生物合成途径。来自不同真菌的HEM25直系同源物能够挽救Hem25? CoQ缺乏，而来自后生生物的HEM25直系同源物则不能。

总之，这项工作揭示了Hem25p驱动线粒体类异戊二烯的大部分转运来用于真菌中CoQ的生物合成。

研究人员表示，CoQ是一种重要的细胞辅助因子，由具有氧化还原活性的醌头基和疏水性聚异丁烯长尾组成。线粒体如何获取细胞质中的类异戊二烯来进行CoQ生物合成一直是个谜。

附：英文原文

Title: Hem25p is required for mitochondrial IPP transport in fungi

Author: Tai, Jonathan, Guerra, Rachel M., Rogers, Sean W., Fang, Zixiang, Muehlbauer, Laura K., Shishkova, Evgenia, Overmyer, Katherine A., Coon, Joshua J., Pagliarini, David J.

Issue&Volume: 2023-10-09

Abstract: Coenzyme Q (CoQ, ubiquinone) is an essential cellular cofactor composed of a redox-active quinone head group and a long hydrophobic polyisoprene tail. How mitochondria access cytosolic isoprenoids for CoQ biosynthesis is a longstanding mystery. Here, via a combination of genetic screening, metabolic tracing and targeted uptake assays, we reveal that Hem25p—a mitochondrial glycine transporter required for haem biosynthesis—doubles as an isopentenyl pyrophosphate (IPP) transporter in Saccharomyces cerevisiae. Mitochondria lacking Hem25p failed to efficiently incorporate IPP into early CoQ precursors, leading to loss of CoQ and turnover of CoQ biosynthetic proteins. Expression of Hem25p in Escherichia coli enabled robust IPP uptake and incorporation into the CoQ biosynthetic pathway. HEM25 orthologues from diverse fungi, but not from metazoans, were able to rescue hem25 CoQ deficiency. Collectively, our work reveals that Hem25p drives the bulk of mitochondrial isoprenoid transport for CoQ biosynthesis in fungi.

DOI: 10.1038/s41556-023-01250-5

Source: https://www.nature.com/articles/s41556-023-01250-5