Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches.

IF 9 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EMBO Molecular Medicine Pub Date : 2024-11-01 Epub Date: 2024-10-28 DOI:10.1038/s44321-024-00155-6
Louise Nuyttens, Jolien Vandewalle, Claude Libert
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Abstract

Sepsis is a heterogeneous syndrome resulting from a dysregulated host response to infection. It is considered as a global major health priority. Sepsis is characterized by significant metabolic perturbations, leading to increased circulating metabolites such as lactate. In mammals, pyruvate is the primary substrate for lactate production. It plays a critical role in metabolism by linking glycolysis, where it is produced, with the mitochondrial oxidative phosphorylation pathway, where it is oxidized. Here, we provide an overview of all cytosolic and mitochondrial enzymes involved in pyruvate metabolism and how their activities are disrupted in sepsis. Based on the available data, we also discuss potential therapeutic strategies targeting these pyruvate-related enzymes leading to enhanced survival.

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败血症诱发的丙酮酸代谢变化:见解和潜在的治疗方法。
败血症是由于宿主对感染的反应失调而导致的一种异质性综合征。它被视为全球主要的健康优先事项。败血症的特点是新陈代谢严重紊乱,导致乳酸等循环代谢物增加。在哺乳动物体内,丙酮酸是产生乳酸的主要底物。丙酮酸在新陈代谢中起着关键作用,它将产生丙酮酸的糖酵解与氧化丙酮酸的线粒体氧化磷酸化途径连接起来。在此,我们概述了参与丙酮酸代谢的所有细胞膜和线粒体酶,以及它们在败血症中的活动是如何被破坏的。根据现有数据,我们还讨论了针对这些丙酮酸相关酶的潜在治疗策略,以提高存活率。
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来源期刊
EMBO Molecular Medicine
EMBO Molecular Medicine 医学-医学:研究与实验
CiteScore
17.70
自引率
0.90%
发文量
105
审稿时长
4-8 weeks
期刊介绍: EMBO Molecular Medicine is an open access journal in the field of experimental medicine, dedicated to science at the interface between clinical research and basic life sciences. In addition to human data, we welcome original studies performed in cells and/or animals provided they demonstrate human disease relevance. To enhance and better specify our commitment to precision medicine, we have expanded the scope of EMM and call for contributions in the following fields: Environmental health and medicine, in particular studies in the field of environmental medicine in its functional and mechanistic aspects (exposome studies, toxicology, biomarkers, modeling, and intervention). Clinical studies and case reports - Human clinical studies providing decisive clues how to control a given disease (epidemiological, pathophysiological, therapeutic, and vaccine studies). Case reports supporting hypothesis-driven research on the disease. Biomedical technologies - Studies that present innovative materials, tools, devices, and technologies with direct translational potential and applicability (imaging technologies, drug delivery systems, tissue engineering, and AI)
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