Rhodosporidium toruloides sir2-like genes remodelled the mitochondrial network to improve the phenotypes of ageing cells

Abstract

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 H2O2 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.