ArticleJournal of cachexia, sarcopenia and muscle2025
Sepsis Induces Long-Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A.
Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Identification of immune cell mitochondrial dysfunction characteristics and clinical predictive biomarkers in sepsis via multi-cohort machine learning and single-cell RNA sequencing.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Deep learning-derived abdominal adiposity phenotypes and 28-day mortality in sepsis.International journal of obesity (2005) · 2026Article
- Beyond the Pump: Unravelling Immunometabolic Crosstalk and Organelle Dynamics in Sepsis-Induced Cardiomyopathy.Journal of cardiovascular translational research · 2026Article
- Impact of the Combination of Epigallocatechin Gallate and Ellagic Acid Supplemented with Ketone Bodies on Energetic Restoration of Mitochondrial Dysfunction and Metabolic Inefficiencies in Patients with Multiple Sclerosis: A Review.International journal of molecular sciences · 2026Review
- Functional and muscle recovery after critical illness: current and future nutritional, physical and metabolic strategies.Annals of intensive care · 2026Review
- Transitions and determinants of ICU-acquired frailty after critical illness: A multicenter cohort study using a multistate Markov model.Annals of intensive care · 2026Article
- Sarcopenia and sepsis fuel a self-perpetuating cycle of immunometabolism decline.Frontiers in immunology · 2026Review
- Gut microbiota-mitochondria-barrier-multiorgan axis: a network-based hypothesis for systemic injury.Frontiers in immunology · 2026Review
- Crosstalk between innate immune signaling pathways and integrated TLR, NLRP3 inflammasome, cGAS-STING, and NF-κB networks in sepsis.Frontiers in cell and developmental biology · 2026Review
- RAGE contributes to persistent sepsis-induced muscle and mitochondrial alterations.Scientific reports · 2025Article
- Sepsis Induces Long-Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A.Journal of cachexia, sarcopenia and muscle · 2025Article
Corrections and comments
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Authors and funding
28 authors.
Funding
Abstract
backgroundSepsis survivors often experience sustained muscle weakness, leading to physical disability, with no pharmacological treatments available. Despite these well-documented long-term clinical consequences, research exploring the cellular and molecular mechanisms is sorely lacking.
methodsBioinformatic analysis was performed in the vastus lateralis transcriptome of human ICU survivors 7 days after ICU discharge (D7), 6 months (M6) and age- and sex-matched controls. Enrichment analysis using Gene Ontology (GO) terms and Mitocarta3.0 was performed at D7 and M6 on differentially expressed genes (DEGs) and modules identified by weighted gene co-expression network analysis (WGCNA). Using a murine model of resuscitated sepsis induced by caecal slurry injection, pathways identified by the bioinformatics analysis were explored in 18- to 24-week-old sepsis-surviving (SS) mice at Day 10. Autophagy flux was investigated both in vivo and in vitro with chloroquine, a lysosomal inhibitor and urolithin A (UA), an autophagy inducer. Systemic metabolism was evaluated with indirect calorimetry, muscle phenotype with in situ and ex vivo contractility, muscle mass, myofibre cross-sectional area and typing and mitochondrial population with transmission electron microscopy (TEM), as well as mitochondrial function with high-resolution respirometry. Autophagic vacuole (AV) level was monitored using LC3B-II and P62 protein expression and TEM.
resultsPathways related to 'mitochondrion' were the only ones whose deregulation persisted between D7 and M6 (p < 0.05) and characterized WGCNA modules correlated with muscle mass, strength and physical function. Shared mitochondrial DEGs between D7 and M6 encoded matrix mitochondrial proteins related to 'metabolism' and 'mitochondrial dynamics'. SS mice exhibited reduced complex I-driven oxygen consumption (CI-J
conclusionMitochondrial and autophagy disruption contributes to long-term muscle dysfunction in human and mouse sepsis survivors. We demonstrate for the first time that sepsis induces an autophagy flux blockade. Urolithin A prevents mitochondrial and muscle impairments both in vivo and in vitro by improving autophagy flux.
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