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

TitleThe mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.
Publication TypeJournal Article
Year of Publication2018
AuthorsHofherr, 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, ERS, Montell, C, Watnick, T, Köttgen, M
JournalPLoS Biol
Date Published2018 08
KeywordsAmino Acid Transport Systems, Acidic, Animals, Antiporters, Calcium, Calcium Channels, Calcium-Binding Proteins, Cilia, Drosophila melanogaster, Heterozygote, Humans, Ion Channels, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Signal Transduction, TRPP Cation Channels, Zebrafish

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.

Alternate JournalPLoS Biol.
Citation Key10.1371/journal.pbio.2005651
PubMed ID30080851
PubMed Central IDPMC6095617
Grant ListP30 DK090868 / DK / NIDDK NIH HHS / United States
R01 EY010852 / EY / NEI NIH HHS / United States
R01 GM073704 / GM / NIGMS NIH HHS / United States
MC_UU_00015/1 / / Medical Research Council / United Kingdom