Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
Cancer Lett. 2017 Apr 1;390:45-47. doi: 10.1016/j.canlet.2017.01.019. Epub 2017 Jan 18.
Succinate is an important intermediate of the tricarboxylic acid (TCA) cycle. In mitochondria, it plays a crucial role in generating adenosine triphosphate. Succinate metabolism is also intertwined with the metabolism of other metabolites and with the "GABA shunt" of the glutamine pathway. Recently, it has become increasingly apparent that the roles of succinate extend into the realms of immunity and cancer. Succinate is a key modulator of the hypoxic response, an important player in tumorigenesis; succinate is also involved in protein succinylation, a novel posttranslational modification pathway. This expanding repertoire of succinate functions suggests that it has broad roles in cellular contexts. Mutations in enzymes such as succinate dehydrogenase (SDH) that participate in succinate-related pathways lead to various pathologies, including tumor formation and innate inflammatory processes. Succinate can have both pro- or anti-tumor effectiveness. Therefore, investigation of succinate as an inflammatory signal may increase our understanding of the cancer-immunity cycle involved in both inflammatory diseases and cancer. Here, we briefly review the emerging roles of succinate, extending beyond metabolism, into anti-cancer immunity. This expansion of succinate roles suggests that it may represent a novel class of regulators in inflammation, which act as key signals in human cancers.
琥珀酸是三羧酸（TCA）循环的重要中间产物。在线粒体中，它在产生三磷酸腺苷（ATP）方面起着至关重要的作用。琥珀酸代谢也与其他代谢物的代谢以及谷氨酰胺途径的“GABA 分流”交织在一起。最近，琥珀酸的作用越来越明显，它延伸到免疫和癌症领域。琥珀酸是缺氧反应的关键调节剂，是肿瘤发生的重要参与者；琥珀酸还参与蛋白质琥珀酰化，这是一种新的翻译后修饰途径。琥珀酸功能的这种扩展组合表明，它在细胞环境中具有广泛的作用。参与琥珀酸相关途径的酶（如琥珀酸脱氢酶（SDH））的突变会导致各种病理，包括肿瘤形成和先天炎症过程。琥珀酸可能具有抗肿瘤或抗癌作用。因此，研究琥珀酸作为炎症信号可能会增加我们对涉及炎症性疾病和癌症的癌症-免疫循环的理解。在这里，我们简要回顾了琥珀酸的新兴作用，它超越了代谢，延伸到了抗癌免疫。琥珀酸作用的这种扩展表明，它可能代表了一类新型的炎症调节剂，作为人类癌症中的关键信号。
