ArticleCritical care (London, England)2018
Plasma mitochondrial DNA and metabolomic alterations in severe critical illness.
Article in Critical care (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
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- Immunometabolic reprogramming in sepsis: mechanisms, clinical endotypes, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Kidney mitochondrial DNA contributes to systemic IL-6 release in sepsis-associated acute kidney injury.JCI insight · 2025Article
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- Early Sepsis Metabolic Changes in Kidney and Liver Precede Clinical Evidence of Organ Dysfunction.American journal of respiratory cell and molecular biology · 2025Article
- Mitochondrial Dysfunction Contributes to Sustained Muscle Loss After Cardiac Surgery: A Prospective Observational Study.Journal of cachexia, sarcopenia and muscle · 2025Observational
- Metabolomic Profiling by UPLC-QTOF/MS Reveals Potential Biomarkers and Metabolic Alterations in Pediatric Septic Shock.Journal of inflammation research · 2025Article
- Personalized Nutrition in the Pediatric ICU: Steering the Shift from Acute Stress to Metabolic Recovery and Rehabilitation.Nutrients · 2024Review
- Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke.Psychosomatic medicine · 2024Article
- Association of mental disorders with sepsis: a bidirectional Mendelian randomization study.Frontiers in public health · 2024Article
- Sustained Perturbation of Metabolism and Metabolic Subphenotypes Are Associated With Mortality and Protein Markers of the Host Response.Critical care explorations · 2023Article
- Plasma metabolic profiling implicates dysregulated lipid metabolism and glycolytic shift in hyperinflammatory ARDS.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality.Journal of clinical medicine · 2022Article
- Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study.Critical care (London, England) · 2022Article
- Minimized Extracorporeal Circulation Is Associated with Reduced Plasma Levels of Free-Circulating Mitochondrial DNA Compared to Conventional Cardiopulmonary Bypass: A Secondary Analysis of an Exploratory, Prospective, Interventional Study.Journal of clinical medicine · 2022Article
- Sex-Specific Catabolic Metabolism Alterations in the Critically Ill following High Dose Vitamin D.Metabolites · 2022Article
- Pharmacometabolomics identifies candidate predictor metabolites of an L-carnitine treatment mortality benefit in septic shock.Clinical and translational science · 2021Article
- Altered lung metabolism and mitochondrial DAMPs in lung injury due to acute kidney injury.American journal of physiology. Lung cellular and molecular physiology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCell-free plasma mitochondrial DNA (mtDNA) levels are associated with endothelial dysfunction and differential outcomes in critical illness. A substantial alteration in metabolic homeostasis is commonly observed in severe critical illness. We hypothesized that metabolic profiles significantly differ between critically ill patients relative to their level of plasma mtDNA.
methodsWe performed a metabolomic study with biorepository plasma samples collected from 73 adults with systemic inflammatory response syndrome or sepsis at a single academic medical center. Patients were treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to plasma NADH dehydrogenase 1 (ND1) mtDNA levels in critical illness, we first generated metabolomic data using gas and liquid chromatography-mass spectroscopy. We performed fold change analysis and volcano plot visualization based on false discovery rate-adjusted p values to evaluate the distribution of individual metabolite concentrations relative to ND1 mtDNA levels. We followed this by performing orthogonal partial least squares discriminant analysis to identify individual metabolites that discriminated ND1 mtDNA groups. We then interrogated the entire metabolomic profile using pathway overrepresentation analysis to identify groups of metabolite pathways that were different relative to ND1 mtDNA levels.
resultsMetabolomic profiles significantly differed in critically ill patients with ND1 mtDNA levels ≥ 3200 copies/μl plasma relative to those with an ND1 mtDNA level < 3200 copies/μl plasma. Several analytical strategies showed that patients with ND1 mtDNA levels ≥ 3200 copies/μl plasma had significant decreases in glycerophosphocholines and increases in short-chain acylcarnitines.
conclusionsDifferential metabolic profiles during critical illness are associated with cell-free plasma ND1 mtDNA levels that are indicative of cell damage. Elevated plasma ND1 mtDNA levels are associated with decreases in glycerophosphocholines and increases in short-chain acylcarnitines that reflect phospholipid metabolism dysregulation and decreased mitochondrial function, respectively.
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Registered trials
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