NAD-dependent protein deacetylase sirtuin-3 (SIRT3)

NAD-dependent protein deacetylase sirtuin-3 (SIRT3) is a member of the mammalian sirtuin family of proteins, homologs to yeast Sir2, and functions as a major mitochondrial protein deacetylase[1]. SIRT3 catalyzes NAD+-dependent removal of acetyl groups from lysine residues on mitochondrial proteins, playing critical roles in regulating mitochondrial metabolism, energy production, cell survival, adaptation to stress, aging, and epigenetic control. SIRT3 deacetylates various substrates, including mitochondrial ribosomal protein MRPL10 and ceramide synthases, thus influencing mitochondrial protein synthesis and ceramide metabolism[4][6]. SIRT3 exists in two isoforms, with the shorter form active in mitochondria and the long isoform found in other cellular compartments[5]. Altered SIRT3 activity is implicated in diverse diseases, including aging-linked disorders, cardiovascular disease, neurodegeneration, metabolic syndromes, and cancer, and it is being evaluated as a therapeutic target and biomarker for mitochondrial function[5][4].

Other names

Sirtuin-3SIRT3NAD-dependent deacetylase sirtuin-3Silent mating type information regulation 2 homolog 3 (S. cerevisiae)SIR2 homolog 3

NAD+-dependent deacetylation of lysine residues on target proteins (removal of acetyl groups using NAD+ as cofactor), regulation of substrate activity (such as ceramide synthases, mitochondrial ribosomal proteins, or histone proteins), possibly mono-ADP-ribosylation[1][6].