Enoyl-CoA hydratase, short chain, 1, mitochondrial (ECHS1)

Enoyl-CoA hydratase, short chain, 1, mitochondrial (ECHS1) is a mitochondrial enzyme that catalyzes the second step in the β-oxidation of fatty acids, specifically hydrating short- to medium-chain trans-2-enoyl-CoA to 3-hydroxyacyl-CoA in the mitochondrial matrix. ECHS1 also plays a role in the catabolism of branched-chain amino acids such as valine and isoleucine, and participates in other metabolic pathways including sphingolipid and ceramide metabolism. ECHS1 deficiency causes the accumulation of toxic intermediates and impaired oxidative phosphorylation, most notably resulting in a form of Leigh syndrome and other mitochondrial disorders. In cancer, ECHS1 is often overexpressed and contributes to tumor cell proliferation, migration, invasion, and chemoresistance by remodeling metabolism, particularly phospholipid and glycosphingolipid pathways. While no currently approved drugs directly target ECHS1 for therapy, it is indirectly implicated in drug resistance mechanisms, and modulation of its pathway (for example, with the glucosylceramide synthase inhibitor Eliglustat) is under investigation in oncology. Biological and clinical significance make ECHS1 both a critical enzyme in metabolism and a potential biomarker or target in cancer and mitochondrial disease contexts.

Other names

Enoyl-CoA hydratase, short chain 1Short-chain enoyl-CoA hydratase 1mECHmECH1SCEHECHS1DEnoyl-CoA hydratase 1Short-chain enoyl-CoA hydrataseEnoyl-CoA hydratase, mitochondrialEpididymis secretory sperm binding proteinEnoyl Coenzyme A hydratase, short chain, 1, mitochondrialCrotonase

Inhibition of glycosphingolipid synthesis (via UGCG inhibition; relevant in ECHS1-dependent cancer metabolism); Targeting ECHS1 function or expression impacts mitochondrial β-oxidation and energy metabolism; in experimental models, knockdown or mutation leads to mitochondrial dysfunction, decreased oxidative phosphorylation, increased drug sensitivity, and apoptosis