title: Mitochondria-type GPAT is required for mitochondrial fusion.
abstract: Glycerol-3-phosphate acyltransferase (GPAT) is involved in the first step in glycerolipid synthesis and is localized in both the endoplasmic reticulum (ER) and mitochondria. To clarify the functional differences between ER-GPAT and mitochondrial (Mt)-GPAT, we generated both GPAT mutants in C. elegans and demonstrated that Mt-GPAT is essential for mitochondrial fusion. Mutation of Mt-GPAT caused excessive mitochondrial fragmentation. The defect was rescued by injection of lysophosphatidic acid (LPA), a direct product of GPAT, and by inhibition of LPA acyltransferase, both of which lead to accumulation of LPA in the cells. Mitochondrial fragmentation in Mt-GPAT mutants was also rescued by inhibition of mitochondrial fission protein DRP-1 and by overexpression of mitochondrial fusion protein FZO-1/mitofusin, suggesting that the fusion/fission balance is affected by Mt-GPAT depletion. Mitochondrial fragmentation was also observed in Mt-GPAT-depleted HeLa cells. A mitochondrial fusion assay using HeLa cells revealed that Mt-GPAT depletion impaired mitochondrial fusion process. We postulate from these results that LPA produced by Mt-GPAT functions not only as a precursor for glycerolipid synthesis but also as an essential factor of mitochondrial fusion.
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Ohba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakuragi
authors.forename: Eriko
authors.initials: E
authors.lastname: Kage-Nakadai
authors.forename: Naoko H
authors.initials: NH
authors.lastname: Tomioka
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.forename: Rieko
authors.initials: R
authors.lastname: Imae
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Naotada
authors.initials: N
authors.lastname: Ishihara
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D063154:Mitochondrial Dynamics; D053142:Mitochondrial Size / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009866:Oogenesis / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D008246:Lysophospholipids; C581914:Acl-6 protein, C elegans; D005992:Glycerol-3-Phosphate O-Acyltransferase; C032881:lysophosphatidic acid