As such, we believe the Sirt3 knockout mice represent a new paradigm that mechanistically links mitochondrial metabolism, the acetylome post-translation signaling network, and age-related disease including ER/PR breast cancer carcinogenesis, radiation-induced liver steatosis, fatty liver, insulin resistance, cardiac hypertrophy, and neurodegenerative diseases. Here, SIRT3 is linked to neurodegenerative disease.