RRC ID 46255
著者 Ohba Y, Sakuragi T, Kage-Nakadai E, Tomioka NH, Kono N, Imae R, Inoue A, Aoki J, Ishihara N, Inoue T, Mitani S, Arai H.
タイトル Mitochondria-type GPAT is required for mitochondrial fusion.
ジャーナル EMBO J
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.
巻・号 32(9)
ページ 1265-79
公開日 2013-5-2
DOI 10.1038/emboj.2013.77
PII emboj201377
PMID 23572076
PMC PMC3642685
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caenorhabditis elegans Proteins / physiology Female Gene Deletion Glycerol-3-Phosphate O-Acyltransferase / genetics Glycerol-3-Phosphate O-Acyltransferase / metabolism* Glycerol-3-Phosphate O-Acyltransferase / physiology Lysophospholipids / metabolism Lysophospholipids / pharmacology Microsomes / metabolism Mitochondria / drug effects Mitochondria / enzymology* Mitochondria / genetics Mitochondrial Dynamics* Mitochondrial Size / drug effects Mitochondrial Size / genetics Models, Biological Mutagenesis, Site-Directed Oogenesis / genetics
IF 9.889
引用数 30
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm3396 tm3452 tm3289 tm3246 tm1133