ArticleJCI insight2021
Metabolic reprogramming during hyperammonemia targets mitochondrial function and postmitotic senescence.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- 3D skeletal muscle model recapitulating the myostatin knockout phenotypic and mitochondrial metabolic features.Physiological reports · 2026Article
- The Muscle-Liver Immunometabolic Axis in Liver Transplantation: A Decisive Role in Outcomes and Mechanisms.International journal of biological sciences · 2026Review
- The Change of Noncoding RNA Expression in Olfactory Bulb of Hepatic Encephalopathy Mouse Model: Transcriptomic Analysis and Cellular Analysis.CNS neuroscience & therapeutics · 2025Article
- Voluntary Activity Wheel Running Improves Hyperammonaemia-Induced Skeletal Muscle Molecular and Metabolic Perturbations in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Integrated Multiomics Analyses of the Molecular Landscape of Sarcopenia in Alcohol-Related Liver Disease.Journal of cachexia, sarcopenia and muscle · 2025Article
- Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.Frontiers in oncology · 2025Review
- Ammonia transporter RhBG initiates downstream signaling and functional responses by activating NFκB.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Differential impact of sex on regulation of skeletal muscle mitochondrial function and protein homeostasis by hypoxia-inducible factor-1α in normoxia.The Journal of physiology · 2024Article
- Clinical and Therapeutic Implications of BCAAs Metabolism during Chronic Liver Disease in Humans: Crosstalk between Skeletal Muscle and Liver.Muscles (Basel, Switzerland) · 2024Review
- Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.Metabolism: clinical and experimental · 2024Article
- Ammonia Toxicity and Associated Protein Oxidation: A Single-Cell Surface Enhanced Raman Spectroscopy Study.Chemical research in toxicology · 2024Article
- L-Isoleucine reverses hyperammonemia-induced myotube mitochondrial dysfunction and post-mitotic senescence.The Journal of nutritional biochemistry · 2024Article
- Instantaneous Inactivation of Herpes Simplex Virus by Silicon Nitride Bioceramics.International journal of molecular sciences · 2023Article
- Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice.Nature communications · 2023Article
- Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin-mediated deacetylation.Aging cell · 2023Article
- Liver transplantation in the patient with physical frailty.Journal of hepatology · 2023Review
- Pain-resolving immune mechanisms in neuropathic pain.Nature reviews. Neurology · 2023Review
- Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease.Journal of cachexia, sarcopenia and muscle · 2023Article
- Microenvironmental ammonia enhances T cell exhaustion in colorectal cancer.Cell metabolism · 2023Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Ammonia is a cytotoxic metabolite with pleiotropic molecular and metabolic effects, including senescence induction. During dysregulated ammonia metabolism, which occurs in chronic diseases, skeletal muscle becomes a major organ for nonhepatocyte ammonia uptake. Muscle ammonia disposal occurs in mitochondria via cataplerosis of critical intermediary metabolite α-ketoglutarate, a senescence-ameliorating molecule. Untargeted and mitochondrially targeted data were analyzed by multiomics approaches. These analyses were validated experimentally to dissect the specific mitochondrial oxidative defects and functional consequences, including senescence. Responses to ammonia lowering in myotubes and in hyperammonemic portacaval anastomosis rat muscle were studied. Whole-cell transcriptomics integrated with whole-cell, mitochondrial, and tissue proteomics showed distinct temporal clusters of responses with enrichment of oxidative dysfunction and senescence-related pathways/proteins during hyperammonemia and after ammonia withdrawal. Functional and metabolic studies showed defects in electron transport chain complexes I, III, and IV; loss of supercomplex assembly; decreased ATP synthesis; increased free radical generation with oxidative modification of proteins/lipids; and senescence-associated molecular phenotype-increased β-galactosidase activity and expression of p16INK, p21, and p53. These perturbations were partially reversed by ammonia lowering. Dysregulated ammonia metabolism caused reversible mitochondrial dysfunction by transcriptional and translational perturbations in multiple pathways with a distinct skeletal muscle senescence-associated molecular phenotype.
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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.