1 Department of Pathology, University of Michigan , Ann Arbor, Michigan.
2 Department of Molecular and Integrative Physiology, University of Michigan , Ann Arbor, Michigan.
Antioxid Redox Signal. 2018 Mar 10;28(8):677-690. doi: 10.1089/ars.2017.7264. Epub 2017 Oct 26.
Developing evidence in the literature suggests that sirtuin 5 (SIRT5) may be involved in metabolic reprogramming, an emerging hallmark of cancer by which neoplastic cells reconfigure their metabolism to support the anabolic demands of rapid cell division. SIRT5 is one of the seven members of the nicotinamide adenine dinucleotide-dependent sirtuin family of lysine deacetylases. It removes succinyl, malonyl, and glutaryl groups from protein targets within the mitochondrial matrix and other subcellular compartments. SIRT5 substrates include a number of proteins integral to metabolism. Recent Advances: New work has begun to elucidate the roles of SIRT5 in glycolysis, tricarboxylic acid cycle, fatty acid oxidation, nitrogen metabolism, pentose phosphate pathway, antioxidant defense, and apoptosis.
In this study, we summarize biological functions of SIRT5 reported in normal tissues and in cancer and discuss potential mechanisms whereby SIRT5 may impact tumorigenesis, particularly focusing on its reported roles in metabolic reprogramming. Finally, we review current efforts to target SIRT5 pharmacologically.
The biological significance of SIRT5 has been elucidated in the context of only an extremely small fraction of its targets and interactors. There is no doubt that further studies in this area will provide a wealth of insights into functions of SIRT5 and its targets in normal and neoplastic cells. Antioxid. Redox Signal. 28, 677-690.
文献中的研究证据表明，SIRT5（烟酰胺腺嘌呤二核苷酸依赖性 Sirtuin 家族的赖氨酸去乙酰化酶的七个成员之一）可能参与代谢重编程，这是癌症的一个新兴标志，其中肿瘤细胞重新配置其代谢以支持快速细胞分裂的合成代谢需求。SIRT5 从线粒体基质和其他细胞区室的蛋白质靶标上去除琥珀酰基、丙二酰基和戊二酰基。SIRT5 的底物包括许多对代谢至关重要的蛋白质。 新进展：新的工作已经开始阐明 SIRT5 在糖酵解、三羧酸循环、脂肪酸氧化、氮代谢、磷酸戊糖途径、抗氧化防御和细胞凋亡中的作用。 关键问题：在这项研究中，我们总结了 SIRT5 在正常组织和癌症中的生物学功能，并讨论了 SIRT5 可能影响肿瘤发生的潜在机制，特别是集中讨论了其在代谢重编程中的报告作用。最后，我们回顾了目前靶向 SIRT5 的药理学努力。 未来方向：SIRT5 的生物学意义仅在其目标和相互作用者的极小部分背景下得到阐明。毫无疑问，该领域的进一步研究将为 SIRT5 及其在正常和肿瘤细胞中的靶标功能提供丰富的见解。抗氧化剂。氧化还原信号。28,677-690。
