MECR, mitochondrial trans-2-enoyl-CoA reductase, is an enzyme in the mitochondrial fatty acid synthesis (mtFAS) pathway [1,2,5,6,7]. mtFAS is essential for respiratory function, generating the octanoic acid precursor for lipoic acid synthesis, and MECR is crucial for the last step of mtFAS [2,5]. MECR also has a role in CD4+ T cell function, oxidative metabolism, and iron and ceramide metabolism [2,4].

In Drosophila, loss-of-function of Mecr causes lethality, and neuronal loss leads to progressive neurodegeneration, with defects in Fe-S cluster biogenesis, increased iron levels, and elevated ceramide levels [2]. In Mecrfl/fl; Cd4cre mice, effector and memory T cells are reduced, and MECR is required for activated CD4+ T cells to proliferate, differentiate, and survive, as Mecr-deficient T cells have decreased mitochondrial respiration, reduced TCA intermediates, and accumulated intracellular iron [4]. In humans, recessive MECR pathogenic variants cause an LHON-like optic neuropathy, a childhood-onset syndromic disorder with dystonia, optic atrophy, and basal ganglia abnormalities, and also adult-onset optic atrophy [1,3,8].

In conclusion, MECR is vital for mtFAS, which is essential for mitochondrial function. Studies using gene-knockout models in Drosophila and mice, as well as human genetic studies, have revealed its role in neurodegeneration, optic neuropathy, and T-cell function. Understanding MECR may provide insights into the mechanisms of these diseases and potential therapeutic targets.