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Hem25p is a mitochondrial IPP transporter

Tai, J.; Guerra, R. M.; Rogers, S. W.; Fang, Z.; Muehlbauer, L. K.; Shishkova, E.; Overmyer, K. A.; Coon, J. J.; Pagliarini, D. J.

2023-03-14 biochemistry
10.1101/2023.03.14.532620 bioRxiv
Show abstract

Coenzyme Q (CoQ, ubiquinone) is an essential cellular cofactor comprised 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 heme biosynthesis--doubles as an isopentenyl pyrophosphate (IPP) transporter in Saccharomyces cerevisiae. Mitochondria lacking Hem25p fail 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 enables robust IPP uptake demonstrating that Hem25p is sufficient for IPP transport. Collectively, our work reveals that Hem25p drives the bulk of mitochondrial isoprenoid transport for CoQ biosynthesis in yeast.

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