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Acetylation of mitochondrial proteins by PD-related neurotoxins or genetic factors. α-syn and MPTP/MPP+ reduce SIRT3 expression, while LRKK2 G2109S inhibits SIRT3 activity by decreasing NAD+ levels to prevent deacetylation of mitochondrial substrates, including SOD2, ATP5B, GS, and IDH2, thereby reducing their activity decline and leading to mitochondrial dysfunction.
