Hofherr, A., Seger, C., Fitzpatrick, F., Busch, T., Michel, E., Luan, J., Osterried, L., Linden, F., Kramer-Zucker, A., Wakimoto, B., Schütze, C., Wiedemann, N., Artati, A., Adamski, J., Walz, G., Kunji, E.R.S., Montell, C., Watnick, T., Köttgen, M. (2018). The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.  PLoS Biol. 16(8): e2005651.

FBrf0239812

Research paper

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.

PMC6095617 (PMC) (EuropePMC)