Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha
{"title":"循环中的 N-乳酰氨基酸和 N-甲酰基蛋氨酸反映线粒体功能障碍并预测脓毒性休克的死亡率。","authors":"Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha","doi":"10.1007/s11306-024-02089-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.</p><p><strong>Objective: </strong>To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.</p><p><strong>Methods: </strong>We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.</p><p><strong>Results: </strong>Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.</p><p><strong>Conclusion: </strong>Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"20 2","pages":"36"},"PeriodicalIF":3.5000,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917846/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.\",\"authors\":\"Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha\",\"doi\":\"10.1007/s11306-024-02089-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.</p><p><strong>Objective: </strong>To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.</p><p><strong>Methods: </strong>We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.</p><p><strong>Results: </strong>Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.</p><p><strong>Conclusion: </strong>Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.</p>\",\"PeriodicalId\":18506,\"journal\":{\"name\":\"Metabolomics\",\"volume\":\"20 2\",\"pages\":\"36\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917846/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11306-024-02089-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11306-024-02089-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.
Introduction: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.
Objective: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.
Methods: We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.
Results: Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.
Conclusion: Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.
期刊介绍:
Metabolomics publishes current research regarding the development of technology platforms for metabolomics. This includes, but is not limited to:
metabolomic applications within man, including pre-clinical and clinical
pharmacometabolomics for precision medicine
metabolic profiling and fingerprinting
metabolite target analysis
metabolomic applications within animals, plants and microbes
transcriptomics and proteomics in systems biology
Metabolomics is an indispensable platform for researchers using new post-genomics approaches, to discover networks and interactions between metabolites, pharmaceuticals, SNPs, proteins and more. Its articles go beyond the genome and metabolome, by including original clinical study material together with big data from new emerging technologies.