The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism

PLoS Biol. 2018 Aug 6;16(8):e2005651. doi: 10.1371/journal.pbio.2005651. eCollection 2018 Aug.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Acidic / metabolism*
  • Animals
  • Antiporters / metabolism
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Cilia / metabolism*
  • Drosophila melanogaster / metabolism
  • Heterozygote
  • Humans
  • Ion Channels / metabolism
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Proteins / metabolism
  • Signal Transduction
  • TRPP Cation Channels / metabolism*
  • Zebrafish


  • ATP-Mg-Pi carrier proteins, mitochondria
  • Amino Acid Transport Systems, Acidic
  • Antiporters
  • Calcium Channels
  • Calcium-Binding Proteins
  • Ion Channels
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • SLC25A25 protein, human
  • TRPP Cation Channels
  • Calcium