Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Free Radic Biol Med. 2019 Apr;134:64-75. doi: 10.1016/j.freeradbiomed.2018.12.036. Epub 2018 Dec 30.
It is known that mitochondria are associated with the ageing process, and the eukaryotic sir2 family of genes significantly affects cellular lifespan. The mammalian sir2 family affects mitochondrial function by regulating targets in different pathways, including oxidative stress, oxidative phosphorylation, and mitochondrial biosynthesis. This study reports that Rt-sirtuin2 and Rt-sirtuin4 genes transfections significantly impacted the lifespan of Rhodosporidium toruloides, and they can significantly improve cellular responses to HO treatment, which induces cell senescence, and restore mitochondrial function. The Rt-sirtuin2 and Rt-sirtuin4 genes increase the expression of the mitochondria-associated proteins Mfn1, Mfn2, and Drp1 and the autophagy-associated proteins LC3-II, LC3-I, Beclin-1 and Parkin and reconstitute mitochondrial networks. Overall, the phenotypic reversal of senescent cells is achieved by regulating mitochondrial viability and mitochondrial autophagy. In vivo experiments with animals also confirmed the improvement of various ageing indexes by the Rt-sirtuin2 and Rt-sirtuin4 genes. Strategies for remodelling mitochondria and improving mitochondrial quality and function can reverse the state of human cells from an ageing phenotype to an active metabolic phenotype. The R. toruloides Sir2 genes can be used to prevent and treat diseases of ageing or mitochondrial dysfunction.
已知线粒体与衰老过程有关，真核生物 sir2 家族的基因显著影响细胞寿命。哺乳动物 sir2 家族通过调节不同途径中的靶标来影响线粒体功能，包括氧化应激、氧化磷酸化和线粒体生物合成。本研究报告称，Rt-sirtuin2 和 Rt-sirtuin4 基因转染显著影响了粘红酵母的寿命，它们可以显著改善细胞对诱导细胞衰老的 HO 处理的反应，并恢复线粒体功能。Rt-sirtuin2 和 Rt-sirtuin4 基因增加了与线粒体相关的蛋白 Mfn1、Mfn2 和 Drp1 以及自噬相关的蛋白 LC3-II、LC3-I、Beclin-1 和 Parkin 的表达，并重建了线粒体网络。总的来说，通过调节线粒体活力和线粒体自噬，可以实现衰老细胞表型的逆转。动物体内实验也证实了 Rt-sirtuin2 和 Rt-sirtuin4 基因改善了各种衰老指标。重塑线粒体和改善线粒体质量和功能的策略可以将人类细胞从衰老表型逆转到活跃的代谢表型。粘红酵母 Sir2 基因可用于预防和治疗衰老或线粒体功能障碍相关疾病。
