ArticleeLife2023
Mitochondrial electron transport chain, ceramide, and coenzyme Q are linked in a pathway that drives insulin resistance in skeletal muscle.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 26 citations in OpenAlex.
- Trial
- Resistance-based training improves mitochondrial capacity and redox balance in aging adults, independent of polyphenol supplementation.Redox biology · 2026Trial
- Age and sex shape plasma lipid associations to skeletal muscle mitochondrial respiration and HGeroScience · 2026Article
- Skeletal Muscle Effects of GLP 1 Receptor Agonists: Molecular Mechanisms and Comparative Insights on Semaglutide and Tirzepatide, a Narrative Review.International journal of molecular sciences · 2026Review
- Comparative Transcriptome Analysis Reveals Tissue-Specific Expression and Conservation of Mitochondrial Metal and Cofactor Genes in Buffalo.Cell biochemistry and biophysics · 2026Article
- Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics.Diabetes & metabolism journal · 2026Review
- A Framework for Selecting Zebrafish Models of Metabolic Diseases: Modeling Strategies, Phenotypic Validation, Mechanistic Investigation, and Efficacy Evaluation.Biomedicines · 2026Review
- Impaired Lung BCAA Metabolism Promotes Ferroptosis and Resultant Pulmonary Arterial Hypertension-Associated Hepatopathy.JACC. Basic to translational science · 2026Article
- The Liver-Testis Axis: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2026Review
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction.Science advances · 2026Article
- Review
- Lipotoxicity in Diabetic Cardiomyopathy: Molecular Basis and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- The long-acting anticoagulant rodenticide brodifacoum induces neuropathology in adult New Zealand White rabbits and is reduced by the bile sequestrant cholestyramine.Neurotoxicology · 2026Article
- Association of Clinical Severity in Autism Spectrum Disorder with Biomolecules Involved in Lipid Metabolism, Inflammation and miRNAs.Biomolecules · 2026Article
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Exploring ceramide as a novel biomarker and therapeutic target for Alzheimer's disease.Frontiers in neuroscience · 2026Review
- TyG index predicts adverse cardiovascular outcomes in patients with multimorbidity of hypertension and obstructive coronary artery disease: a cohort study.Frontiers in cardiovascular medicine · 2026Article
- Molecular pathways, tissue-specific roles, and therapeutic opportunities in mitochondrial resilience-based strategies for insulin resistance.Frontiers in clinical diabetes and healthcare · 2026Review
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Insulin resistance (IR) is a complex metabolic disorder that underlies several human diseases, including type 2 diabetes and cardiovascular disease. Despite extensive research, the precise mechanisms underlying IR development remain poorly understood. Previously we showed that deficiency of coenzyme Q (CoQ) is necessary and sufficient for IR in adipocytes and skeletal muscle (Fazakerley et al., 2018). Here, we provide new insights into the mechanistic connections between cellular alterations associated with IR, including increased ceramides, CoQ deficiency, mitochondrial dysfunction, and oxidative stress. We demonstrate that elevated levels of ceramide in the mitochondria of skeletal muscle cells result in CoQ depletion and loss of mitochondrial respiratory chain components, leading to mitochondrial dysfunction and IR. Further, decreasing mitochondrial ceramide levels in vitro and in animal models (mice, C57BL/6J) (under chow and high-fat diet) increased CoQ levels and was protective against IR. CoQ supplementation also rescued ceramide-associated IR. Examination of the mitochondrial proteome from human muscle biopsies revealed a strong correlation between the respirasome system and mitochondrial ceramide as key determinants of insulin sensitivity. Our findings highlight the mitochondrial ceramide-CoQ-respiratory chain nexus as a potential foundation of an IR pathway that may also play a critical role in other conditions associated with ceramide accumulation and mitochondrial dysfunction, such as heart failure, cancer, and aging. These insights may have important clinical implications for the development of novel therapeutic strategies for the treatment of IR and related metabolic disorders.
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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.