Identification and characterization of Eci3, a murine kidney‐specific Δ³, Δ²‐enoyl‐CoA isomerase

Abstract

Oxidation of unsaturated fatty acids requires the action of auxiliary enzymes, such as Δ(3),Δ(2)-enoyl-CoA isomerases. Here we describe a detailed biochemical, molecular, histological, and evolutionary characterization of Eci3, the fourth member of the mammalian enoyl-CoA isomerase family. Eci3 specifically evolved in rodents after gene duplication of Eci2. Eci3 is with 79% identity homologous to Eci2 and contains a peroxisomal targeting signal type 1. Subcellular fractionation of mouse kidney and immunofluorescence studies revealed a specific peroxisomal localization for Eci3. Expression studies showed that mouse Eci3 is almost exclusively expressed in kidney. By using immunohistochemistry, we found that Eci3 is not only expressed in cells of the proximal tubule, but also in a subset of cells in the tubulointerstitium and the glomerulus. In vitro, Eci3 catalyzed the isomerization of trans-3-nonenoyl-CoA to trans-2-nonenoyl-CoA equally efficient as Eci2, suggesting a role in oxidation of unsaturated fatty acids. However, in contrast to Eci2, in silico gene coexpression and enrichment analysis for Eci3 in kidney did not yield carboxylic acid metabolism, but diverse biological functions, such as ion transport (P=7.1E-3) and tissue morphogenesis (P=1.0E-3). Thus, Eci3 picked up a novel and unexpected role in kidney function during rodent evolution.

Human Δ3,Δ2‐enoyl‐CoA isomerase, type 2: a structural enzymology study on the catalytic role of its ACBP domain and helix‐10

“…The kinetic properties of each of these isomerases from rat have been reported, showing a broad range of fatty acyl chain length specificities and different kinetic parameters for 3Z‐ and 3E‐enoyl‐CoA substrates . Rodents possess a third mitochondrial ECI, which has been identified recently and which is homologous to ECI2 . Structures have been described for ECI1 from rat mitochondria (1XX4) and human mitochondria (1SG4) , MFE1 from rat peroxisomes (2X58) and ECI from yeast peroxisomes (1PJH) .…”

Single-Cell Atlas Reveals Fatty Acid Metabolites Regulate the Functional Heterogeneity of Mesenchymal Stem Cells

“…Our scRNA-seq data shows that pre-MSCs significantly enriched stemness genes (such as Hp1bp3 and Baz1b) and FA metabolic genes (such as Eci2 and Pam) (Satani et al, 2003;Dutta et al, 2014;van Weeghel et al, 2014;Zanella et al, 2019). Conversely, lineage-committed MSCs dominantly enriched differentiation genes (such as Col27a1 and Jund) and proliferation genes (such as Fgfr1 and Mafb) (Naito et al, 2005;Naba et al, 2017;Ardizzone et al, 2020;Guo et al, 2020) (Figure 2A).…”

Cedrol, a Major Component of Cedarwood Oil, Ameliorates High‐Fat Diet‐Induced Obesity in Mice

“…[ 41 ] Eci3 , the fourth member of the mammalian enoyl‐CoA isomerase family, catalyzes the isomerization of trans‐3‐nonenoyl‐CoA to trans‐2‐nonenoyl‐CoA, suggesting a role in the oxidation of unsaturated fatty acids. [ 42 ] Echdc2 is essential for metabolizing fatty acids to produce both acetyl‐CoA and energy, which is named for its sequence similarity to the enoyl‐CoA hydratase domain. [ 43 ] Taken together, the anti‐obesity effect of CED might be associated with the upregulation of Pparα , Acsm3 , Eci3 , and Echdc2 expression in WAT.…”