Mouse Cth/Cse loss with cysteine-free diet: molecular mechanisms & dependencies

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What it does

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Recorded relationships

What it acts on

Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism.
Mouse Cth/Cse loss with cysteine-free diet → Urinary intermediary-metabolite loss in cysteine-depleted mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse tissue/urine metabolomics during combined genetic and dietary depletion.
limitations
Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The shortage affected how efficiently the animal retained and used fuel.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 316–322
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse tissue/urine metabolomics during combined genetic and dietary depletion. · source_derived_draft · unverified_draft
## l-cysteine-depletion-carbon-loss The shortage affected how efficiently the animal retained and used fuel. Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism. Model: Mouse tissue/urine metabolomics during combined genetic and dietary depletion. Limitations: Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence
Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes.
Mouse Cth/Cse loss with cysteine-free diet → Tissue coenzyme A during mouse cysteine depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7.
limitations
CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 308–314
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. · source_derived_draft · unverified_draft
## l-cysteine-depletion-coa A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant. Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes. Model: Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. Limitations: CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence

The events it takes part in

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Situations it appears in

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Mouse Cth/Cse loss with cysteine-free diet