SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK1/Parkin Mitophagy Dysfunction

## 1. Molecular Mechanism and Rationale SIRT3 is the primary mitochondrial NAD⁺-dependent deacetylase, responsible for maintaining the activity of over 100 mitochondrial proteins through lysine deacetylation. In cortical projection neurons—particularly Layer II/III excitatory neurons of the entorhinal cortex (EC)—SIRT3 activity is critical because these neurons have exceptionally high metabolic demands: they maintain extensive axonal arbors projecting to hippocampus and neocortex, requiring sus...