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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.*

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

PLoS Biol. 16:e2005651 (2018)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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/Pisolute 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Polycystic Kidney-disease; Left-right Asymmetry; Left-right Axis; Intracellular Calcium; Kupffers Vesicle; Drosophila-melanogaster; Endoplasmic-reticulum; Embryonic-development; Zebrafish Pronephros; Membrane-proteins
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1544-9173
e-ISSN 1545-7885
Zeitschrift PLoS Biology
Quellenangaben Band: 16, Heft: 8, Seiten: , Artikelnummer: e2005651 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort 1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500600-001
DOI 10.1371/journal.pbio.2005651
WOS ID WOS:000443383300017
Scopus ID 85053237333
PubMed ID 30080851
Erfassungsdatum 2018-09-05
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