期刊
PLOS BIOLOGY
卷 16, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.2005651
关键词
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资金
- Deutsche Forschungsgemeinschaft [SFB 1140, SFB/TRR 152]
- Excellence Initiative of the German Federal Government (Spemann Graduate School) [GSC-4, EXC 294 BIOSS]
- Excellence Initiative of the German State Government (Spemann Graduate School) [GSC-4, EXC 294 BIOSS]
- European Research Council [648235]
- NIH [R01 GM073704, R01 EY010852]
- Medical Research Council, UK [MC_UU_00015/1]
- European Research Council (ERC) [648235] Funding Source: European Research Council (ERC)
- MRC [MC_UU_00015/1] Funding Source: UKRI
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 Ca(2+)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.
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