Hydroxyacylglutathione hydrolase, mitochondrial

Hydroxyacylglutathione hydrolase, mitochondrial (HAGH) is a thiolesterase that catalyzes hydrolysis of S-D-lactoyl-glutathione to glutathione and D-lactic acid (UniProt: Q16775). The enzyme plays a role in cellular detoxification and metabolic homeostasis through glutathione metabolism, a critical antioxidant system in mitochondria.

HAGH is a mitochondrial protein involved in glyoxalase-related metabolism. No primary disease associations are documented in UniProt records. However, glutathione metabolism and mitochondrial function are implicated in neurodegeneration, and dysregulation of detoxification pathways is relevant to neurodegenerative disease pathophysiology.

In Alzheimer's disease, HAGH is downregulated in post-mortem human AD brain tissue relative to age-matched controls (mean log2 fold-change: −0.18; Chaparral AD proteomics). This modest but consistent reduction was detected across post-mortem brain fractions using TMT-labeled quantitative proteomics, suggesting impaired mitochondrial glutathione metabolism may contribute to AD-associated oxidative stress and energetic dysfunction.