Modulation of serotonin signaling by the putative oxaloacetate decarboxylase FAHD-1 in Caenorhabditis elegans
Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1...
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| creator | Baraldo, Giorgia Etemad, Solmaz Weiss, Alexander K H Jansen-Dürr, Pidder Mack, Hildegard I D |
| description | Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1's function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. Finally, we propose a model to explain how a metabolic defect could ultimately lead to marked changes in neuronal signaling. |
| doi_str_mv | 10.1371/journal.pone.0220434 |
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The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1's function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Baraldo et al 2019 Baraldo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e61d38145d53f7af9c9ff6a7684684753da79caac0cd134c57021c9aade24a793</citedby><cites>FETCH-LOGICAL-c692t-e61d38145d53f7af9c9ff6a7684684753da79caac0cd134c57021c9aade24a793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693844/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693844/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31412049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Yildirim, Arda</contributor><creatorcontrib>Baraldo, Giorgia</creatorcontrib><creatorcontrib>Etemad, Solmaz</creatorcontrib><creatorcontrib>Weiss, Alexander K H</creatorcontrib><creatorcontrib>Jansen-Dürr, Pidder</creatorcontrib><creatorcontrib>Mack, Hildegard I D</creatorcontrib><title>Modulation of serotonin signaling by the putative oxaloacetate decarboxylase FAHD-1 in Caenorhabditis elegans</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. 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The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1's function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. 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| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abnormalities Aging Animals Animals, Genetically Modified Behavior, Animal - drug effects Behavior, Animal - physiology Biology Biology and Life Sciences Biosynthesis Caenorhabditis elegans Caenorhabditis elegans Proteins - genetics Caenorhabditis elegans Proteins - metabolism Carboxy-Lyases - genetics Carboxy-Lyases - metabolism Cellular signal transduction Decarboxylases Depletion Dopamine Dopamine - pharmacology E coli Egg laying Enzyme activation Enzymes Eukaryotes Fumaric acid Fumarylacetoacetase Genetics Hydrolases Locomotion Locomotion - drug effects Locomotion - physiology Medicine and Health Sciences Metabolism Metabolites Mitochondria Mitochondria - genetics Mitochondria - metabolism Nematodes Nervous system Neurons Neurons - drug effects Neurons - metabolism Neurotransmitters Novels Oxaloacetate decarboxylase Phenols (Class of compounds) Physical Sciences Physiological aspects Physiology Plasmids Protein turnover Proteins Research and Analysis Methods Serotonin Serotonin - metabolism Serotonin - pharmacology Signal Transduction - drug effects Signal Transduction - physiology Signaling Worms |
| title | Modulation of serotonin signaling by the putative oxaloacetate decarboxylase FAHD-1 in Caenorhabditis elegans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T00%3A18%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Modulation%20of%20serotonin%20signaling%20by%20the%20putative%20oxaloacetate%20decarboxylase%20FAHD-1%20in%20Caenorhabditis%20elegans&rft.jtitle=PloS%20one&rft.au=Baraldo,%20Giorgia&rft.date=2019-08-14&rft.volume=14&rft.issue=8&rft.spage=e0220434&rft.epage=e0220434&rft.pages=e0220434-e0220434&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0220434&rft_dat=%3Cgale_plos_%3EA596448902%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2273182613&rft_id=info:pmid/31412049&rft_galeid=A596448902&rft_doaj_id=oai_doaj_org_article_18befc3000004e1f98397155a70bf540&rfr_iscdi=true |