title: Impaired fatty acid oxidation in a Drosophila model of mitochondrial trifunctional protein (MTP) deficiency.
abstract: Mitochondrial trifunctional protein (MTP), which consists of the MTPα and MTPβ subunits, catalyzes long-chain fatty acid β-oxidation. MTP deficiency in humans results in Reye-like syndrome. Here, we generated Drosophila models of MTP deficiency by targeting two genes encoding Drosophila homologs of human MTPα and MTPβ, respectively. Both Mtpα(KO) and Mtpβ(KO) flies were viable, but demonstrated reduced lifespan, defective locomotor activity, and reduced fecundity represented by the number of eggs laid by the females. The phenotypes of Mtpα(KO) flies were generally more striking than those of Mtpβ(KO) flies. Mtpα(KO) flies were hypersensitive to fasting, and retained lipid droplets in their fat body cells as in non-fasting conditions. The amount of triglyceride was also unchanged upon fasting in Mtpα(KO) flies, suggesting that lipid mobilization was disrupted. Finally, we showed that both Mtpα(KO) and Mtpβ(KO) flies accumulated acylcarnitine and hydroxyacylcarnitine, diagnostic markers of MTP deficiencies in humans. Our results indicated that both Mtpα(KO) and Mtpβ(KO) flies were impaired in long-chain fatty acid β-oxidation. These flies should be useful as a model system to investigate the molecular pathogenesis of MTP deficiency.
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kishita
authors.forename: Manabu
authors.initials: M
authors.lastname: Tsuda
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D055786:Gene Knockout Techniques; D008928:Mitochondria / Q000201:enzymology*; D063991:Mitochondrial Trifunctional Protein; D023421:Models, Animal; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D029721:Drosophila Proteins; D005227:Fatty Acids; D009097:Multienzyme Complexes; D063991:Mitochondrial Trifunctional Protein