title: 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.
authors.affiliation: 1Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mt. Sinai, 1425 Madison Ave., Box 1498, New York, NY 10029, USA. sander.houten@mssm.edu.
authors.forename: Michel
authors.initials: M
authors.lastname: van Weeghel
authors.forename: Rob
authors.initials: R
authors.lastname: Ofman
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Argmann
authors.forename: Jos P N
authors.initials: JP
authors.lastname: Ruiter
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.forename: Saskia V
authors.initials: SV
authors.lastname: Oussoren
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Jan
authors.initials: J
authors.lastname: Aten
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D064006:Dodecenoyl-CoA Isomerase / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D051379:Mice
chemical_list: D017931:DNA Primers; D064006:Dodecenoyl-CoA Isomerase
keywords: fatty acid oxidation; gene duplication; peroxisomes