Hydroxyacyl-thioester dehydratase type 2, mitochondrial (HTD2)

Hydroxyacyl-thioester dehydratase type 2 (HTD2) is a mitochondrial enzyme essential for the mitochondrial fatty acid synthesis (mtFAS) pathway, catalyzing the dehydration of 3-hydroxyacyl-ACP to trans-2-enoyl-ACP. This step is crucial for the endogenous production of lipoic acid, a cofactor for multiple mitochondrial enzyme complexes. HTD2 deficiency results in impaired complex I activity, elevated oxidative stress, and disrupted adipocyte insulin sensitivity. Its principal biological role spans maintaining mitochondrial respiratory competence, lipid metabolism regulation, and overall mitochondrial health[1][3][7]. Downregulation or genetic deficiency of HTD2 is implicated in metabolic disorders, mitochondrial dysfunction, and possibly rare neurodevelopmental syndromes. Lipoic acid supplementation can mitigate dysfunction due to HTD2 deficiency[1]. HTD2 is considered a potential therapeutic target for diseases linked to mitochondrial and metabolic abnormalities.

Other names

HTD2Hydroxyacyl-thioester dehydratase type 2, mitochondrial3-hydroxyacyl-[acyl-carrier-protein] dehydratase (rare, yeast-specific context)HsHTD2

Restoration of mitochondrial function through lipoic acid supplementation (by bypassing endogenous synthesis suppressed by HTD2 deficiency). Possibly inhibition or modulation in future enzyme-targeted therapies for metabolic disease (no approved drugs yet).