Fig. 6.

Schematic diagram of the action mechanism SIRT1 inhibition on mitochondrial dysfunction. The inhibition of SIRT1 induces acetylation of mitochondrial Ca²⁺ transporter, MCU, promoting mitochondrial Ca²⁺ overload, ROS burst and loss of mitochondrial membrane potential. Global acetylation of mitochondrial proteins due to SIRT1 inhibition obstructs their ubiquitin and LC3-labeling, preventing mitophagy-associated clearance, and ultimately causing cell apoptosis.