title: Docosahexaenoic acid mediates peroxisomal elongation, a prerequisite for peroxisome division.
abstract: Peroxisome division is regulated by several factors, termed fission factors, as well as the conditions of the cellular environment. Over the past decade, the idea of metabolic control of peroxisomal morphogenesis has been postulated, but remains largely undefined to date. In the current study, docosahexaenoic acid (DHA, C22:6n-3) was identified as an inducer of peroxisome division. In fibroblasts isolated from patients that carry defects in peroxisomal fatty acid β-oxidation, peroxisomes are much less abundant than normal cells. Treatment of these patient fibroblasts with DHA induced the proliferation of peroxisomes to the level seen in normal fibroblasts. DHA-induced peroxisomal proliferation was abrogated by treatment with a small inhibitory RNA (siRNA) targeting dynamin-like protein 1 and with dynasore, an inhibitor of dynamin-like protein 1, which suggested that DHA stimulates peroxisome division. DHA augmented the hyper-oligomerization of Pex11pβ and the formation of Pex11pβ-enriched regions on elongated peroxisomes. Time-lapse imaging analysis of peroxisomal morphogenesis revealed a sequence of steps involved in peroxisome division, including elongation in one direction followed by peroxisomal fission. DHA enhanced peroxisomal division in a microtubule-independent manner. These results suggest that DHA is a crucial signal for peroxisomal elongation, a prerequisite for subsequent fission and peroxisome division.
authors.affiliation: Graduate School of Systems Life Sciences, Faculty of Sciences, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Itoyama
authors.forename: Masanori
authors.initials: M
authors.lastname: Honsho
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Abe
authors.forename: Ann
authors.initials: A
authors.lastname: Moser
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiki
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000172:deficiency / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D034281:Dynamins; D004746:Enoyl-CoA Hydratase / Q000172:deficiency / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007535:Isomerases / Q000172:deficiency / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000172:deficiency / Q000378:metabolism; D010084:Oxidation-Reduction; D063994:Peroxisomal Bifunctional Enzyme; D018901:Peroxisomal Disorders / Q000378:metabolism / Q000473:pathology; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D055503:Protein Multimerization / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D059008:Time-Lapse Imaging
chemical_list: D005227:Fatty Acids; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; C490453:PEX11B protein, human; C486345:PEX16 protein, human; D034741:RNA, Small Interfering; D004281:Docosahexaenoic Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases