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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 Ca 2+  signals into respective physiological functions are unknown. Here, we show that the Ca 2+ -regulated mitochondrial ATP-Mg/P i  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 Ca 2+  establishing an evolutionarily conserved molecular link between ciliary signaling and mitochondrial metabolism.

The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism