SIRT3 is a mitochondrial NAD+-dependent deacetylase that regulates cellular energy metabolism through protein deacetylation of key metabolic enzymes including SOD2, PDHA1, and ATP synthase components 1. Beyond its classical deacetylase activity, SIRT3 functions as a protein-lysine deacylase, catalyzing debenzoylation and delactylation of substrates such as CCNE2 and histone H4 23. In response to metabolic stress, SIRT3 deacetylates the transcription factor FOXO3 to promote mitochondrial DNA transcription 4, while regulating hepatic ceramide metabolism and lipogenesis 5. Beyond mitochondrial functions, SIRT3 consolidates heterochromatin and stabilizes nuclear integrity through interaction with nuclear envelope proteins, counteracting senescence in mesenchymal stem cells 6. SIRT3 protects against oxidative stress-induced ferroptosis by activating the SIRT3/FoxO3a pathway and increasing SOD2 and catalase expression to reduce ROS generation 7. The deubiquitinase USP11 stabilizes SIRT3 through deubiquitination, protecting against ferroptosis in intervertebral disc degeneration 8. Clinically, SIRT3 downregulation associates with hepatocellular carcinoma progression, where SIRT3 activation suppresses HCC cell growth by delactylating CCNE2 2. In glioblastoma, SIRT3 inhibition sensitizes cells to ferroptosis through mitophagy promotion and SLC7A11 downregulation 9, suggesting SIRT3 as a therapeutic target across multiple malignancies.