NAD-dependent protein deacetylase (    ). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (   , ). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5PO (  ). Contributes to the regulation of the cellular energy metabolism . Important for regulating tissue-specific ATP levels . In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription . 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 (By similarity). Regulates hepatic lipogenesis. 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.
Subcellular locations: Mitochondrion matrix
Widely expressed.