Sirt3
Function
NAD-dependent protein deacetylase (PubMed:17923681, PubMed:18794531, PubMed:21172655, PubMed:23835326, PubMed:26620563). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:17923681, PubMed:18794531, PubMed:21172655, PubMed:23835326). Known targets include ACSS1, IDH, GDH, PDHA1, SOD2, LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16790548, PubMed:18794531, PubMed:21172655). Contributes to the regulation of the cellular energy metabolism (PubMed:23835326, PubMed:36804859). Important for regulating tissue-specific ATP levels (PubMed:18794531, PubMed:24252090). In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription (PubMed:23283301). Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation (PubMed:26620563). Regulates hepatic lipogenesis (PubMed:36804859). Uses NAD(+) substrate imported by SLC25A47, triggering downstream activation of PRKAA1/AMPK-alpha signaling cascade that ultimately downregulates sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance (PubMed:36804859). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating delactylation of proteins, such as CCNE2 and 'Lys-16' of histone H4 (H4K16la) (By similarity).
Sequence Similarities
Belongs to the sirtuin family. Class I subfamily.
Tissue Specificity
Expressed in cardiomyocytes (at protein level) (PubMed:11056054, PubMed:35959657). Expressed in the brain, liver, kidney and testes (PubMed:11056054). Expressed in skeletal muscles (at protein level) (PubMed:23283301, PubMed:23835326).
Cellular localization
- Isoform L
- Mitochondrion matrix
- Isoform S
- Cytoplasm
Alternative names
Sir2l3, Sirt3, NAD-dependent protein deacetylase sirtuin-3, NAD-dependent protein delactylase sirtuin-3, Regulatory protein SIR2 homolog 3, SIR2-like protein 3, mSIR2L3