The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.
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 molecul...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-08-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.2005651 |
| _version_ | 1818361544728117248 |
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| author | Alexis Hofherr Claudia Seger Fiona Fitzpatrick Tilman Busch Elisabeth Michel Jingting Luan Lea Osterried Frieder Linden Albrecht Kramer-Zucker Barbara Wakimoto Conny Schütze Nils Wiedemann Anna Artati Jerzy Adamski Gerd Walz Edmund R S Kunji Craig Montell Terry Watnick Michael Köttgen |
| author_facet | Alexis Hofherr Claudia Seger Fiona Fitzpatrick Tilman Busch Elisabeth Michel Jingting Luan Lea Osterried Frieder Linden Albrecht Kramer-Zucker Barbara Wakimoto Conny Schütze Nils Wiedemann Anna Artati Jerzy Adamski Gerd Walz Edmund R S Kunji Craig Montell Terry Watnick Michael Köttgen |
| author_sort | Alexis Hofherr |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T21:18:23Z |
| format | Article |
| id | doaj.art-fb76b96ee34346ac93852c1d9cd88af5 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-13T21:18:23Z |
| publishDate | 2018-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-fb76b96ee34346ac93852c1d9cd88af52022-12-21T23:31:11ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852018-08-01168e200565110.1371/journal.pbio.2005651The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.Alexis HofherrClaudia SegerFiona FitzpatrickTilman BuschElisabeth MichelJingting LuanLea OsterriedFrieder LindenAlbrecht Kramer-ZuckerBarbara WakimotoConny SchützeNils WiedemannAnna ArtatiJerzy AdamskiGerd WalzEdmund R S KunjiCraig MontellTerry WatnickMichael KöttgenCilia 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.https://doi.org/10.1371/journal.pbio.2005651 |
| spellingShingle | Alexis Hofherr Claudia Seger Fiona Fitzpatrick Tilman Busch Elisabeth Michel Jingting Luan Lea Osterried Frieder Linden Albrecht Kramer-Zucker Barbara Wakimoto Conny Schütze Nils Wiedemann Anna Artati Jerzy Adamski Gerd Walz Edmund R S Kunji Craig Montell Terry Watnick Michael Köttgen The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. PLoS Biology |
| title | The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. |
| title_full | The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. |
| title_fullStr | The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. |
| title_full_unstemmed | The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. |
| title_short | The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. |
| title_sort | mitochondrial transporter slc25a25 links ciliary trpp2 signaling and cellular metabolism |
| url | https://doi.org/10.1371/journal.pbio.2005651 |
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