How Does Sirt3 Regulate Ddh2

In a recent proteomic study with human cell lines over a dozen of MDH2 acetylated lysine residues have been identified. Identification of Sirt3 as putative deacetylase which regulates MDH2 acetylation suggests that Sirt3 may regulate MDH2 function via lysine deacetylation.
It has been discovered that four lysine residues of MDH2 are acetylated, and acetylation has been shown to activate MDH2. Acetylation of MDH2 promotes the association with GOT2, which stimulates the malate shuttle activity and promotes the net transfer of cytosolic NADH into mitochondria to support ATP production.

Inhibition of the malate-aspartate shuttle by a specific inhibitor, amino oxyacetate, was found to impair the conversion of glucose into products of the tricarboxylic