Zhang Wenhui, Lang Ren
Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.
Front Cell Dev Biol. 2023 Sep 22;11:1266973. doi: 10.3389/fcell.2023.1266973. eCollection 2023.
Succinate serves as an essential circulating metabolite within the tricarboxylic acid (TCA) cycle and functions as a substrate for succinate dehydrogenase (SDH), thereby contributing to energy production in fundamental mitochondrial metabolic pathways. Aberrant changes in succinate concentrations have been associated with pathological states, including chronic inflammation, ischemia/reperfusion (IR) injury, and cancer, resulting from the exaggerated response of specific immune cells, thereby rendering it a central area of investigation. Recent studies have elucidated the pivotal involvement of succinate and SDH in immunity beyond metabolic processes, particularly in the context of cancer. Current scientific endeavors are concentrated on comprehending the functional repercussions of metabolic modifications, specifically pertaining to succinate and SDH, in immune cells operating within a hypoxic milieu. The efficacy of targeting succinate and SDH alterations to manipulate immune cell functions in hypoxia-related diseases have been demonstrated. Consequently, a comprehensive understanding of succinate's role in metabolism and the regulation of SDH is crucial for effectively targeting succinate and SDH as therapeutic interventions to influence the progression of specific diseases. This review provides a succinct overview of the latest advancements in comprehending the emerging functions of succinate and SDH in metabolic processes. Furthermore, it explores the involvement of succinate, an intermediary of the TCA cycle, in chronic inflammation, IR injury, and cancer, with particular emphasis on the mechanisms underlying succinate accumulation. This review critically assesses the potential of modulating succinate accumulation and metabolism within the hypoxic milieu as a means to combat various diseases. It explores potential targets for therapeutic interventions by focusing on succinate metabolism and the regulation of SDH in hypoxia-related disorders.
琥珀酸是三羧酸（TCA）循环中一种重要的循环代谢物，作为琥珀酸脱氢酶（SDH）的底物发挥作用，从而在基本的线粒体代谢途径中促进能量产生。琥珀酸浓度的异常变化与包括慢性炎症、缺血/再灌注（IR）损伤和癌症在内的病理状态相关，这些病理状态是由特定免疫细胞的过度反应引起的，因此使其成为一个核心研究领域。最近的研究阐明了琥珀酸和SDH在代谢过程之外的免疫中的关键作用，特别是在癌症背景下。目前的科学努力集中在理解代谢修饰对在缺氧环境中运作的免疫细胞的功能影响，特别是与琥珀酸和SDH相关的影响。针对琥珀酸和SDH改变以操纵缺氧相关疾病中免疫细胞功能的有效性已得到证实。因此，全面了解琥珀酸在代谢中的作用以及SDH的调节对于有效地将琥珀酸和SDH作为治疗干预靶点以影响特定疾病的进展至关重要。本综述简要概述了理解琥珀酸和SDH在代谢过程中新兴功能的最新进展。此外，它探讨了TCA循环中间产物琥珀酸在慢性炎症、IR损伤和癌症中的作用，特别强调了琥珀酸积累的潜在机制。本综述批判性地评估了在缺氧环境中调节琥珀酸积累和代谢作为对抗各种疾病手段的潜力。它通过关注缺氧相关疾病中琥珀酸代谢和SDH的调节来探索治疗干预的潜在靶点。
