PLoS Biology (Aug 2018)

The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.

  • Alexis Hofherr,
  • Claudia Seger,
  • Fiona Fitzpatrick,
  • Tilman Busch,
  • Elisabeth Michel,
  • Jingting Luan,
  • Lea Osterried,
  • Frieder Linden,
  • Albrecht Kramer-Zucker,
  • Barbara Wakimoto,
  • Conny Schütze,
  • Nils Wiedemann,
  • Anna Artati,
  • Jerzy Adamski,
  • Gerd Walz,
  • Edmund R S Kunji,
  • Craig Montell,
  • Terry Watnick,
  • Michael Köttgen

DOI
https://doi.org/10.1371/journal.pbio.2005651
Journal volume & issue
Vol. 16, no. 8
p. e2005651

Abstract

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Cilia are organelles specialized in movement and signal transduction. The ciliary transient receptor potential ion channel polycystin-2 (TRPP2) controls elementary cilia-mediated physiological functions ranging from male fertility and kidney development to left-right patterning. However, the molecular components translating TRPP2 channel-mediated Ca2+ signals into respective physiological functions are unknown. Here, we show that the Ca2+-regulated mitochondrial ATP-Mg/Pi solute carrier 25 A 25 (SLC25A25) acts downstream of TRPP2 in an evolutionarily conserved metabolic signaling pathway. We identify SLC25A25 as an essential component in this cilia-dependent pathway using a genome-wide forward genetic screen in Drosophila melanogaster, followed by a targeted analysis of SLC25A25 function in zebrafish left-right patterning. Our data suggest that TRPP2 ion channels regulate mitochondrial SLC25A25 transporters via Ca2+ establishing an evolutionarily conserved molecular link between ciliary signaling and mitochondrial metabolism.