Hem25p is required for mitochondrial IPP transport in fungi

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)1616-1624
Number of pages9
JournalNature Cell Biology
Volume25
Issue number11
DOIs
StatePublished - Nov 2023

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