Fig. 6: ABHD11 regulation of OGDHc activity. | Nature Communications

Fig. 6: ABHD11 regulation of OGDHc activity.

From: ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex

Fig. 6

Working model for functional lipoylation of the OGDHc. a Cyclical reduction and oxidation of lipoate is required for OGDHc catalytic activity, and this process requires ABHD11 which associates with the OGDHc, maintaining functional lipoylation and allowing the conversion of 2-OG to succinyl CoA. b When ABHD11 is depleted or inhibited, lipoyl adducts form, preventing functional lipoylation. These adducts may arise from lipid peroxidation products (e.g. 4-HNE) formed by ROS generated by the OGDHc or by the electron transport chain, or by other as yet undefined mechanisms. Loss of functional lipoylation leads to 2-OG accumulation and the formation of L-2-HG, which can inhibit 2-OG dependent dioxygenases involved in the HIF response and DNA hydroxymethylation.

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