Characterization of HACD1 K64Q mutant found in arrhythmogenic right ventricular dysplasia patients

概要

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Arrhythmogenic right ventricular dysplasia (ARVD) is an autosomal dominant heart disease. A K64Q mutation was found in ARVD-affected individuals in the HACD1 gene, which encodes an enzyme involved in very long-chain fatty acid (VLCFA) elongation, although any relationship between mutation and pathology remained unclear. Here, we demonstrate that HACD1 (K64Q) exhibits normal enzyme activity, intracellular localization, and interaction with other VLCFA enzymes, with no dominant negative effect on VLCFA elongation. Thus, it appears unlikely that this mutation is ARVD-causative. Moreover, through these analyses we found that HACD1 interacts with KAR and TER, the reductase enzymes involved in the second and fourth VLCFA elongation cycle, respectively. This finding indicates that the enzymes responsible for the VLCFA elongation cycle form an elongase complex.
Oxford University Pressの論文
2010-11-01