NAD-dependent protein deacetylase (PubMed:23835326, PubMed:17923681, PubMed:18794531, PubMed:21172655, PubMed:26620563). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:23835326, PubMed:17923681, PubMed:18794531, PubMed:21172655). 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). 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). H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide Binds 1 zinc ion per subunit. Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (By similarity). Interacts with NDUFA9, ACSS1, IDH2 and GDH (By similarity). Interacts with PCCA (PubMed:23438705). Strongly expressed in liver and kidney (PubMed:11056054). Expressed in skeletal muscles (at protein level) (PubMed:23283301, PubMed:23835326). Weakly expressed in lung (PubMed:11056054). Sirt3 expression decreases by 50% in skeletal muscle upon fasting. Decreased muscle endurance under energetically demanding conditions (PubMed:24252090). Decreased Mn-SOD activity in liver, increased mitochondrial superoxide levels and genomic instability upon exposure to ionizing radiations (PubMed:21172655). In vivo ATP levels are reduced by 50 % in organs that normally express high levels of this protein (PubMed:18794531). ATP levels are unchanged in organs that normally express low levels of this protein (PubMed:18794531). Leads to increased mitochondrial protein acetylation (PubMed:18794531). Decreased ceramide accumulation in brain mitochondria (PubMed:26620563). Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo. Belongs to the sirtuin family. Class I subfamily.