Hem25p is required for mitochondrial IPP transport in fungi

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 increment CoQ deficiency. Collectively, our work reveals that Hem25p drives the bulk of mitochondrial isoprenoid transport for CoQ biosynthesis in fungi. Tai et al. show that Hem25p-a mitochondrial glycine transporter required for haem biosynthesis-is also needed for isopentenyl pyrophosphate (IPP) transport into mitochondria and coenzyme Q synthesis in Saccharomyces cerevisiae.

Automated summary

The study reveals that Hem25p, a mitochondrial glycine transporter required for haem biosynthesis, also acts as an isopentenyl pyrophosphate (IPP) transporter in Saccharomyces cerevisiae, playing a crucial role in coenzyme Q synthesis.