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

Kurt Warnhoff, Thomas W Hercher, Ralf R Mendel, Gary Ruvkun

Genes & development 2021 Feb 01

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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. © 2021 Warnhoff et al.; Published by Cold Spring Harbor Laboratory Press.

Citation

Kurt Warnhoff, Thomas W Hercher, Ralf R Mendel, Gary Ruvkun. Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans. Genes & development. 2021 Feb 01;35(3-4):212-217