De novo NAD+ synthesis is ineffective for NAD+ supply in axenically cultured Caenorhabditis elegans
Abstract To secure an adequate nicotinamide adenine dinucleotide (NAD+) supply for survival, organisms typically rely on two complementary mechanisms: the de novo synthesis pathway and the salvage pathway. Notably, the classic quinolinic acid phosphoribosyltransferase (QPRTase) for de novo NAD+ synt...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07984-2 |
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| Summary: | Abstract To secure an adequate nicotinamide adenine dinucleotide (NAD+) supply for survival, organisms typically rely on two complementary mechanisms: the de novo synthesis pathway and the salvage pathway. Notably, the classic quinolinic acid phosphoribosyltransferase (QPRTase) for de novo NAD+ synthesis is absent in Caenorhabditis elegans (C. elegans), despite the reported alternative mechanism involving uridine monophosphate phosphoribosyltransferase (UMPS). However, the effectiveness of this proposed mechanism for NAD+ production of C. elegans remains unclear. Here, using a chemically defined medium, we observed that removing NAD+ salvage precursors from the medium results in a significant decrease in NAD+ levels, causing severe developmental delay and fecundity loss in C. elegans. Strikingly, these defects cannot be restored by any metabolites from the de novo synthesis pathway, including the direct QPRTase substrate quinolinic acid (QA). Furthermore, the deficiency of umps-1 does not cause any significant changes in the NAD+ levels of C. elegans. Moreover, the growth defects of the umps-1 mutant could be rescued by uridine, but not the salvage NAD+ supply. Additionally, we discovered that commercially available QA products contain substantial amounts of nicotinic acid, potentially producing misleading information. Collectively, our results demonstrate that C. elegans lacks the necessary mechanisms for de novo synthesis of NAD+. |
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| ISSN: | 2399-3642 |