A review on SIRT3 and its natural small molecule activators as a potential Preventive and therapeutic target

Sirtuins (SIRTs) were originally characterized by yeast Sir2 as a lifespan regulator that is conserved in all three structural domains of bacteria, archaea and eukaryotes and belong to histone deacetylases consisting of seven members (SIRT1-SIRT7). Surprisingly, SIRTs have been shown to play important regulatory roles in almost all cellular functions, including mitochondrial biogenesis, oxidative stress, inflammation, cell growth, energy metabolism, neural function, and stress resistance. Among the SIRT members, sirtuin 3 (SIRT3) is one of the most important deacetylases that regulates the mitochondrial acetylation and plays a role in pathological processes, such as metabolism, DNA repair, oxidative stress, apoptosis and ferroptosis. Therefore, SIRT3 is considered as a potential target for the treatment of a variety of pathological diseases, including metabolic diseases, neurodegenerative diseases, age-related diseases and others. Furthermore, the isolation, screening, and development of SIRT3 signaling agonists, especially from natural products, have become a widely investigated objective. This paper describes the structure of SIRT3 protein, discusses the pathological process of SIRT3-mediated acetylation modification, and reviews the role of SIRT3 in diseases, SIRT3 activators and its related disease studies.