Fmp30p is a mitochondrial phosphatidylinositol hydrolase that modulates CoQ biosynthesis

  • Nat Commun. 2026 May 30. doi: 10.1038/s41467-026-73766-x.
Zakery N Baker  #  1 ,  Rachel M Guerra  #  1 ,  Sean W Rogers  1 ,  David J Pagliarini  2  3  4  5
Affiliations
  • 1. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
  • 2. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA. [email protected].
  • 3. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA. [email protected].
  • 4. Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. [email protected].
  • 5. Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO, USA. [email protected].
  • # Contributed equally.
PMID: 42218121 DOI: 10.1038/s41467-026-73766-x
Abstract

Organellar membranes feature bespoke lipid compositions; however, the Enzymes that craft these compositions and the functional implications these lipids exert on membrane protein organization and activity are insufficiently understood. Here, we discover that the inner mitochondrial membrane protein Fmp30p, a member of the Metallo-β-lactamase superfamily, displays Phospholipase type D activity toward phosphatidylinositol (PI)-a notable mitochondrial membrane component with unclear functional roles. FMP30 deletion caused substantial and specific elevation of PI species in purified mitochondria. Augmenting mitochondrial PI levels in this way, or by targeting established PI-modifying Enzymes to the organelle, increased coenzyme Q (CoQ) biosynthesis concomitant with elevated expression of CoQ-related Enzymes and enhanced CoQ metabolon formation. Collectively, our work establishes Fmp30p as a mitochondrial PI Phospholipase related to CoQ biology and reveals the broader importance of inner membrane PI in regulating mitochondrial function.

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