Obtaining the necessary molybdenum cofactor for sulfite oxidase activity in the nematode Caenorhabditis elegans surprisingly involves a dietary source

Oliphant, Kevin D.; Fettig, Robin R.; Snoozy, Jennifer; Mendel, Ralf R.; Warnhoff, Kurt

doi:10.1016/j.jbc.2022.102736

Cited by 5 publications

(1 citation statement)

References 35 publications

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“…However, animals carrying the suox-1(gk738847) hypomorphic allele are healthy under standard culture conditions (33, 34). suox-1(gk738847) mutant animals display only 4% SUOX-1 activity compared to wild type and are exquisitely sensitive to sulfite stress (55). Thus, the suox-1(gk738847) mutation creates a sensitized genetic background to probe for increases in endogenous sulfite production.…”

Section: Resultsmentioning

confidence: 99%

Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis inCaenorhabditis elegans

Warnhoff

Snoozy

Breen

et al. 2023

Preprint

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The amino acid cysteine is critical for many aspects of life, yet excess cysteine is toxic. Therefore, animals require pathways to maintain cysteine homeostasis. In mammals, high cysteine activates cysteine dioxygenase, a key enzyme in cysteine catabolism. The mechanism by which cysteine dioxygenase is regulated remains largely unknown. We discovered thatC. eleganscysteine dioxygenase (cdo-1) is transcriptionally activated by high cysteine and the hypoxia inducible transcription factor (hif-1).hif-1-dependent activation ofcdo-1occurs downstream of an H2S-sensing pathway that includesrhy-1,cysl-1, andegl-9.cdo-1transcription is primarily activated in the hypodermis where it is sufficient to drive sulfur amino acid metabolism. EGL-9 and HIF-1 are core members of the cellular hypoxia response. However, we demonstrate that the mechanism of HIF-1-mediated induction ofcdo-1functions largely independent of EGL-9 prolyl hydroxylation and the von Hippel-Lindau E3 ubiquitin ligase; classical hypoxia signaling pathway components. We propose that the intersection ofhif-1andcdo-1reveals a negative feedback loop for maintaining cysteine homeostasis. High cysteine stimulates the production of an H2S signal. H2S then activates therhy-1/cysl-1/egl-9signaling pathway, increasing HIF-1-mediated transcription ofcdo-1, promoting degradation of cysteine via CDO-1.

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Section: Resultsmentioning

confidence: 99%

Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis inCaenorhabditis elegans

Warnhoff

Snoozy

Breen

et al. 2023

Preprint

Self Cite

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The Final Step in Molybdenum Cofactor Biosynthesis—A Historical View

Mendel,

Oliphant

2024

Molecules

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Molybdenum (Mo) is an essential micronutrient across all kingdoms of life, where it functions as a key component of the active centers of molybdenum-dependent enzymes. For these enzymes to gain catalytic activity, Mo must be complexed with a pterin scaffold to form the molybdenum cofactor (Moco). The final step of Moco biosynthesis is catalyzed by the enzyme Mo-insertase. This review focuses on eukaryotic Mo-insertases, with an emphasis on those found in plants and mammals, which have been instrumental in advancing the understanding of Mo biochemistry. Additionally, a historical perspective is provided, tracing the discovery of Mo-insertase from the early 1960s to the detailed characterization of its reaction mechanism in 2021. This review also highlights key milestones in the study of Mo-insertase, including mutant characterization, gene cloning, structural elucidation at the atomic level, functional domain assignment, and the spatial organization of the enzyme within cellular protein networks.

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Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis in Caenorhabditis elegans

Warnhoff

Snoozy

Breen

et al. 2024

eLife

Self Cite

View full text Add to dashboard Cite

The amino acid cysteine is critical for many aspects of life, yet excess cysteine is toxic. Therefore, animals require pathways to maintain cysteine homeostasis. In mammals, high cysteine activates cysteine dioxygenase, a key enzyme in cysteine catabolism. The mechanism by which cysteine dioxygenase is regulated remains largely unknown. We discovered that C. elegans cysteine dioxygenase (cdo-1) is transcriptionally activated by high cysteine and the hypoxia inducible transcription factor (hif-1). hif-1- dependent activation of cdo-1 occurs downstream of an H2S-sensing pathway that includes rhy-1, cysl-1, and egl-9. cdo-1 transcription is primarily activated in the hypodermis where it is sufficient to drive sulfur amino acid metabolism. EGL-9 and HIF-1 are core members of the cellular hypoxia response. However, we demonstrate that the mechanism of HIF-1-mediated induction of cdo-1 functions largely independent of EGL-9 prolyl hydroxylation and the von Hippel-Lindau E3 ubiquitin ligase; classical hypoxia signaling pathway components. We propose that the intersection of hif-1 and cdo-1 reveals a negative feedback loop for maintaining cysteine homeostasis. High cysteine stimulates the production of an H2S signal. H2S then activates the rhy-1/cysl-1/egl-9 signaling pathway, increasing HIF-1-mediated transcription of cdo-1, promoting degradation of cysteine via CDO-1.

show abstract

Obtaining the necessary molybdenum cofactor for sulfite oxidase activity in the nematode Caenorhabditis elegans surprisingly involves a dietary source

Cited by 5 publications

References 35 publications

Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis inCaenorhabditis elegans

Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis inCaenorhabditis elegans

The Final Step in Molybdenum Cofactor Biosynthesis—A Historical View

Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis in Caenorhabditis elegans

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