mot-1 Encodes a Putative Molybdate Transporter Required for Embryonic Viability in C. elegans — 62a — Robin Fettig, Sushila Bhattacharya, Jennifer Snoozy

Molybdenum is an essential trace metal that is required for the synthesis of the molybdenum cofactor (Moco). Moco is required for animal life and is synthesized through an ancient and conserved biosynthetic pathway. In the final step of Moco synthesis, molybdenum insertase uses bioavailable molybdate to insert molybdenum into the MPT-AMP precursor, forming mature Moco. Despite well-characterized mechanisms of molybdate transport in prokaryotes, fungi, and plants, how animal cells acquire essential molybdenum for Moco synthesis remains mysterious. By searching for distant homologs of plant molybdate transporters encoded by the C. elegans genome, we uncovered a transmembrane anion transporter that we have named molybdate transporter 1 (mot-1). mot-1 is required for embryonic viability when animals are deprived of dietary Moco, suggesting a role for MOT-1 in promoting endogenous Moco synthesis. Furthermore, the embryonic lethality caused by mot-1 loss of function is bypassed by supplemental molybdate, suggesting a defect in molybdate transport. Furthermore, the embryonic lethality displayed by mot-1 mutant animals is suppressed by inactivating mutations in cth-2 or cdo-1, established suppressors of Moco-deficient lethality. Finally, mot-1 mutant embryos display reduced Moco content, as detected by the enzymatic activity of the Moco-requiring sulfite oxidase enzyme. Together, these genetic and biochemical data suggest the model that MOT-1 is a C. elegans molybdate transport protein that is required for promoting embryonic Moco homeostasis and viability. This is the first description of an animal molybdate transporter and lays the foundation for understanding molybdate transport in higher eukaryotes such as humans.

University of South Dakota
Kurt Warnhoff