TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - van Weeghel, Michel A1 - te Brinke, Heleen A1 - van Lenthe, Henk A1 - Kulik, Wim A1 - Minkler, Paul E. A1 - Stoll, Maria S. K. A1 - Sass, Jörn Oliver A1 - Janssen, Uwe A1 - Stoffel, Wilhelm A1 - Schwab, K. Otfried A1 - Wanders, Ronald J. A. A1 - Hoppel, Charles L. A1 - Houten, Sander M. T1 - Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids JF - FASEB J. (FASEB Journal) N2 - Mitochondrial enoyl-CoA isomerase (ECI1) is an auxiliary enzyme involved in unsaturated fatty acid oxidation. In contrast to most of the other enzymes involved in fatty acid oxidation, a deficiency of ECI1 has yet to be identified in humans. We used wild-type (WT) and Eci1-deficient knockout (KO) mice to explore a potential presentation of human ECI1 deficiency. Upon food withdrawal, Eci1-deficient mice displayed normal blood β-hydroxybutyrate levels (WT 1.09 mM vs. KO 1.10 mM), a trend to lower blood glucose levels (WT 4.58 mM vs. KO 3.87 mM, P=0.09) and elevated blood levels of unsaturated acylcarnitines, in particular C12:1 acylcarnitine (WT 0.03 μM vs. KO 0.09 μM, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12:1 acylcarnitine levels (WT 0.01 μM vs. KO 0.04 μM, P<0.01). Overall, the phenotypic presentation of Eci1-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Eci1-deficient fibroblasts caused a more pronounced accumulation of C12:1 acylcarnitine on incubation with unsaturated fatty acids (12-fold, P<0.05). We conclude that Eci2 compensates for Eci1 deficiency explaining the mild phenotype of Eci1-deficient mice. Hypoglycemia and accumulation of C12:1 acylcarnitine might be diagnostic markers to identify ECI1 deficiency in humans. Y1 - 2012 SN - 0892-6638 SS - 0892-6638 U6 - https://doi.org/10.1096/fj.12-206326 DO - https://doi.org/10.1096/fj.12-206326 PM - 22782973 VL - 26 IS - 10 SP - 4316 EP - 4326 ER -