Title | The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | 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, ERS, Montell, C, Watnick, T, Köttgen, M |
Journal | PLoS Biol |
Volume | 16 |
Issue | 8 |
Pagination | e2005651 |
Date Published | 2018 08 |
ISSN | 1545-7885 |
Keywords | Amino 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 |
Abstract | 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. |
DOI | 10.1371/journal.pbio.2005651 |
Alternate Journal | PLoS Biol. |
Citation Key | 10.1371/journal.pbio.2005651 |
PubMed ID | 30080851 |
PubMed Central ID | PMC6095617 |
Grant List | P30 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 |