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Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans

The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display le...

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Autores principales: Warnhoff, Kurt, Hercher, Thomas W., Mendel, Ralf R., Ruvkun, Gary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849362/
https://www.ncbi.nlm.nih.gov/pubmed/33446569
http://dx.doi.org/10.1101/gad.345579.120
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author Warnhoff, Kurt
Hercher, Thomas W.
Mendel, Ralf R.
Ruvkun, Gary
author_facet Warnhoff, Kurt
Hercher, Thomas W.
Mendel, Ralf R.
Ruvkun, Gary
author_sort Warnhoff, Kurt
collection PubMed
description The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematode Caenorhabditis elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a C. elegans model of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency.
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spelling pubmed-78493622021-08-01 Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans Warnhoff, Kurt Hercher, Thomas W. Mendel, Ralf R. Ruvkun, Gary Genes Dev Research Communication The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematode Caenorhabditis elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a C. elegans model of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency. Cold Spring Harbor Laboratory Press 2021-02-01 /pmc/articles/PMC7849362/ /pubmed/33446569 http://dx.doi.org/10.1101/gad.345579.120 Text en © 2021 Warnhoff et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Warnhoff, Kurt
Hercher, Thomas W.
Mendel, Ralf R.
Ruvkun, Gary
Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans
title Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans
title_full Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans
title_fullStr Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans
title_full_unstemmed Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans
title_short Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans
title_sort protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient c. elegans
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849362/
https://www.ncbi.nlm.nih.gov/pubmed/33446569
http://dx.doi.org/10.1101/gad.345579.120
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