Ski3/TTC37 deficiency associated with trichohepatoenteric syndrome causes mitochondrial dysfunction in Drosophila.

Autor: Ohnuma K; Department of Biological Sciences, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji-shi, Japan., Kishita Y; Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Japan., Nyuzuki H; Department of Pediatrics, School of Medicine, Niigata University, Asahimachi, Japan., Kohda M; Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Japan., Ohtsu Y; Division of Medical Nutrition, Faculty of Healthcare, Tokyo Healthcare University, Setagaya-ku, Japan., Takeo S; Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji-shi, Japan., Asano T; Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji-shi, Japan., Sato-Miyata Y; Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji-shi, Japan.; Research and Education Centre for Natural Sciences, Keio University, Yokohama, Japan., Ohtake A; Department of Pediatrics & Clinical Genomics, Saitama Medical University, Iruma-gun, Japan., Murayama K; Department of Metabolism, Center for Medical Genetics, Chiba Children's Hospital, Midori-ku, Japan., Okazaki Y; Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Japan., Aigaki T; Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji-shi, Japan.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2020 Apr 15. Date of Electronic Publication: 2020 Apr 15.
DOI: 10.1002/1873-3468.13792
Abstrakt: Tetratricopeptide repeat protein 37 (TTC37) is a causative gene of trichohepatoenteric syndrome (THES). However, little is known about the pathogenesis of this disease. Here, we characterize the phenotype of a Drosophila model in which ski3, a homolog of TTC37, is disrupted. The mutant flies are pupal lethal, and the pupal lethality is partially rescued by transgenic expression of wild-type ski3 or human TTC37. The mutant larvae show growth retardation, heart arrhythmia, triacylglycerol accumulation, and aberrant metabolism of glycolysis and the TCA cycle. Moreover, mitochondrial membrane potential and respiratory chain complex activities are significantly reduced in the mutants. Our results demonstrate that ski3 deficiency causes mitochondrial dysfunction, which may underlie the pathogenesis of THES.
(© 2020 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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