ArticleNature metabolism2024
Regulation of urea cycle by reversible high-stoichiometry lysine succinylation.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- Succinylation modification in diabetes and diabetic complications: Mechanisms and functions (Review).Molecular medicine reports · 2026Review
- Targeting MFF succinylation: a novel therapeutic strategy for premature ovarian insufficiency by restoring mitochondrial dynamics in granulosa cells.Journal of ovarian research · 2026Review
- Generation of High-Quality Succinyl Spectral Libraries for Improved Proteome-Wide Succinylome Analysis Using Data-Independent Acquisition.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- ASS1 facilitates T-ALL progression via the arginine-mediated mTORC1/c-Myc signaling pathway.Scientific reports · 2025Article
- SIRT5-mediated desuccinylation of MTHFD2 enhances chemoresistance in breast cancer cells by reducing therapy-induced senescence.Communications biology · 2025Article
- Mechanisms of metabolism-coupled protein modifications.Nature chemical biology · 2025Review
- Crosstalk between metabolism and epigenetics during macrophage polarization.Epigenetics & chromatin · 2025Review
- Posttranslational Regulation of Mammalian Sulfur Amino Acid Metabolism.International journal of molecular sciences · 2025Review
- Changes of intestinal microbiota and liver metabolomics in yellow catfish (Frontiers in microbiology · 2025Article
- Protein succinylation, hepatic metabolism, and liver diseases.World journal of hepatology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
The post-translational modification lysine succinylation is implicated in the regulation of various metabolic pathways. However, its biological relevance remains uncertain due to methodological difficulties in determining high-impact succinylation sites. Here, using stable isotope labelling and data-independent acquisition mass spectrometry, we quantified lysine succinylation stoichiometries in mouse livers. Despite the low overall stoichiometry of lysine succinylation, several high-stoichiometry sites were identified, especially upon deletion of the desuccinylase SIRT5. In particular, multiple high-stoichiometry lysine sites identified in argininosuccinate synthase (ASS1), a key enzyme in the urea cycle, are regulated by SIRT5. Mutation of the high-stoichiometry lysine in ASS1 to succinyl-mimetic glutamic acid significantly decreased its enzymatic activity. Metabolomics profiling confirms that SIRT5 deficiency decreases urea cycle activity in liver. Importantly, SIRT5 deficiency compromises ammonia tolerance, which can be reversed by the overexpression of wild-type, but not succinyl-mimetic, ASS1. Therefore, lysine succinylation is functionally important in ammonia metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.