RRC ID 66172
Author Warnhoff K, Hercher TW, Mendel RR, Ruvkun G.
Title Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans.
Journal Genes Dev
Abstract 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 Celegans 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.
Volume 35(3-4)
Pages 212-217
Published 2021-2-1
DOI 10.1101/gad.345579.120
PII gad.345579.120
PMID 33446569
PMC PMC7849362
MeSH Animals Bacteria / metabolism Biological Transport Caenorhabditis elegans / metabolism* Coenzymes / administration & dosage* Coenzymes / deficiency Coenzymes / pharmacokinetics Humans Metal Metabolism, Inborn Errors / therapy* Metalloproteins / administration & dosage* Metalloproteins / deficiency Metalloproteins / pharmacokinetics Molybdenum Cofactors Protein Binding Pteridines / administration & dosage* Pteridines / pharmacokinetics
IF 9.527
Prokaryotes E. coli BW25113 JW0764