Department of Respiratory and Critical Care Medicine, Department of Breast Surgery, Department of Outpatient, and Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Theranostics. 2024 May 11;14(7):2993-3013. doi: 10.7150/thno.97320. eCollection 2024.
The sirtuin (SIRT) family is well-known as a group of deacetylase enzymes that rely on nicotinamide adenine dinucleotide (NAD). Among them, mitochondrial SIRTs (SIRT3, SIRT4, and SIRT5) are deacetylases located in mitochondria that regulate the acetylation levels of several key proteins to maintain mitochondrial function and redox homeostasis. Mitochondrial SIRTs are reported to have the Janus role in tumorigenesis, either tumor suppressive or oncogenic functions. Although the multi-faceted roles of mitochondrial SIRTs with tumor-type specificity in tumorigenesis, their critical functions have aroused a rising interest in discovering some small-molecule compounds, including inhibitors and activators for cancer therapy. Herein, we describe the molecular structures of mitochondrial SIRTs, focusing on elucidating their regulatory mechanisms in carcinogenesis, and further discuss the recent advances in developing their targeted small-molecule compounds for cancer therapy. Together, these findings provide a comprehensive understanding of the crucial roles of mitochondrial SIRTs in cancer and potential new therapeutic strategies.
Sirtuin（SIRT）家族是一组依赖烟酰胺腺嘌呤二核苷酸（NAD）的去乙酰化酶，其中线粒体 SIRTs（SIRT3、SIRT4 和 SIRT5）是位于线粒体中的去乙酰化酶，可调节几种关键蛋白质的乙酰化水平，以维持线粒体功能和氧化还原平衡。线粒体 SIRTs 在肿瘤发生中具有双面作用，既有肿瘤抑制作用，也有致癌作用。尽管线粒体 SIRTs 在肿瘤发生中具有肿瘤类型特异性的多方面作用，但它们的关键功能引起了人们对发现一些小分子化合物的兴趣，包括用于癌症治疗的抑制剂和激活剂。本文描述了线粒体 SIRTs 的分子结构，重点阐明了它们在致癌作用中的调节机制，并进一步讨论了开发针对这些小分子化合物的靶向癌症治疗方法的最新进展。总之，这些发现为线粒体 SIRTs 在癌症中的关键作用以及潜在的新治疗策略提供了全面的认识。
