Mecr, the mitochondrial trans-2-enoyl-CoA reductase, is a key enzyme in the mitochondrial fatty acid synthesis (mtFAS) pathway [1,2,4,5,6]. MtFAS is essential for respiratory function, and Mecr is required for the last step of this process [2,4]. This pathway has a significant impact on various biological processes, including lipid metabolism, and is crucial for normal cellular function [2]. Genetic models, such as those in yeast and flies, have been valuable in studying Mecr [1,2,4].

In Drosophila, loss of function of Mecr leads to lethality, and neuronal loss causes progressive neurodegeneration. There is a defect in Fe-S cluster biogenesis, increased iron levels, and elevated ceramide levels, with reduction of either iron or ceramide suppressing the neurodegenerative phenotypes [2]. In humans, mutations in Mecr cause pediatric-onset neurodegeneration, with fibroblasts showing elevated ceramide levels and impaired iron homeostasis [2]. In yeast, a MECR-R258W mutant shows impaired oxidative growth, reduced oxygen consumption rate, decreased protein levels, lack of lipoylation of key metabolic enzymes, and increased sensitivity to H2O2 treatment [1]. In Mecrfl/fl; Cd4cre mice, effector and memory T cells are reduced, and Mecr-deficient T cells have decreased mitochondrial respiration, reduced TCA intermediates, accumulated intracellular iron, and fitness disadvantages in inflammatory, tumor, and infection models [3].

In conclusion, Mecr is essential for mtFAS, which in turn is crucial for mitochondrial function, lipid and iron metabolism, and immune cell function. Studies using knockout models in flies, yeast, and mice have revealed its role in neurodegenerative diseases and T-cell-related processes, providing insights into potential disease mechanisms and therapeutic targets [1,2,3].