Reference - Detail
| RRC ID | 76256 |
|---|---|
| Author | Oliphant KD, Fettig RR, Snoozy J, Mendel RR, Warnhoff K. |
| Title | Obtaining the necessary molybdenum cofactor for sulfite oxidase activity in the nematode Caenorhabditis elegans surprisingly involves a dietary source. |
| Journal | J Biol Chem |
| Abstract |
Molybdenum cofactor (Moco) is a prosthetic group necessary for the activity of four unique enzymes, including the essential sulfite oxidase (SUOX-1). Moco is required for life; humans with inactivating mutations in the genes encoding Moco-biosynthetic enzymes display Moco deficiency, a rare and lethal inborn error of metabolism. Despite its importance to human health, little is known about how Moco moves among and between cells, tissues, and organisms. The prevailing view is that cells that require Moco must synthesize Moco de novo. Although, the nematode Caenorhabditis elegans appears to be an exception to this rule and has emerged as a valuable system for understanding fundamental Moco biology. C. elegans has the seemingly unique capacity to both synthesize its own Moco as well as acquire Moco from its microbial diet. However, the relative contribution of Moco from the diet or endogenous synthesis has not been rigorously evaluated or quantified biochemically. We genetically removed dietary or endogenous Moco sources in C. elegans and biochemically determined their impact on animal Moco content and SUOX-1 activity. We demonstrate that dietary Moco deficiency dramatically reduces both animal Moco content and SUOX-1 activity. Furthermore, these biochemical deficiencies have physiological consequences; we show that dietary Moco deficiency alone causes sensitivity to sulfite, the toxic substrate of SUOX-1. Altogether, this work establishes the biochemical consequences of depleting dietary Moco or endogenous Moco synthesis in C. elegans and quantifies the surprising contribution of the diet to maintaining Moco homeostasis in C. elegans. |
| Volume | 299(1) |
| Pages | 102736 |
| Published | 2023-1-1 |
| DOI | 10.1016/j.jbc.2022.102736 |
| PII | S0021-9258(22)01179-6 |
| PMID | 36423681 |
| PMC | PMC9793310 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Diet Metal Metabolism, Inborn Errors Metalloproteins* / genetics Metalloproteins* / metabolism Molybdenum / metabolism Molybdenum Cofactors* / metabolism Pteridines / metabolism Sulfite Oxidase* / genetics Sulfite Oxidase* / metabolism |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | FX30167 FX30168 |