Pathological cardiac hypertrophy is associated with reduced intracellular NAD+ levels (134), and reduced SIRT3 activity could feed forward to further impair and cause damage to complex I. SIRT3 is positively linked not only to electron transport chain (ETC) and tricarboxylic acid (TCA) cycle activities (135, 136), but mitochondrial anti-oxidant defenses by increasing SOD2 activity (137) and maintaining mitochondrial GSH levels (138). Here, SIRT3 is linked to cardiac hypertrophy.