Succinate dehydrogenase (SDH) has been classically considered a mitochondrial enzyme with the unique property to participate in both the citric acid cycle and the electron transport chain. However, in recent years, several studies have highlighted the role of the SDH substrate, i.e. succinate, in biological processes other than metabolism, tumorigenesis being the most remarkable. For this reason, SDH has now been defined a tumor suppressor and succinate an oncometabolite. In this review, we discuss recent findings regarding alterations in SDH activity leading to succinate accumulation, which include SDH mutations, regulation of mRNA expression, post-translational modifications and endogenous SDH inhibitors. Further, we report an extensive examination of the role of succinate in cancer development through the induction of epigenetic and metabolic alterations and the effects on epithelial to mesenchymal transition, cell migration and invasion, and angiogenesis. Finally, we have focused on succinate and SDH as diagnostic markers for cancers having altered SDH expression/activity.

中文翻译：

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琥珀酸脱氢酶的调节和琥珀酸在癌症中的作用。

琥珀酸脱氢酶（SDH）通常被认为是线粒体酶，具有参与柠檬酸循环和电子传输链的独特特性。然而，近年来，一些研究强调了SDH底物，即琥珀酸，在代谢以外的生物过程中的作用，最显着的是肿瘤发生。由于这个原因，SDH现在已被定义为一种肿瘤抑制因子，琥珀酸酯为一种合成代谢物。在这篇综述中，我们讨论有关导致琥珀酸积累的SDH活性变化的最新发现，包括SDH突变，mRNA表达调节，翻译后修饰和内源性SDH抑制剂。进一步，我们报告了琥珀酸酯通过表观遗传和代谢变化的诱导以及对上皮向间充质转化，细胞迁移和侵袭以及血管生成的影响，广泛研究了琥珀酸酯在癌症发展中的作用。最后，我们集中于琥珀酸盐和SDH作为已改变SDH表达/活性的癌症的诊断标记。