title: Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis.
abstract: Plasmalogen biosynthesis is regulated by modulating fatty acyl-CoA reductase 1 stability in a manner dependent on cellular plasmalogen level. However, physiological significance of the regulation of plasmalogen biosynthesis remains unknown. Here we show that elevation of the cellular plasmalogen level reduces cholesterol biosynthesis without affecting the isoprenylation of proteins such as Rab and Pex19p. Analysis of intermediate metabolites in cholesterol biosynthesis suggests that the first oxidative step in cholesterol biosynthesis catalyzed by squalene monooxygenase (SQLE), an important regulator downstream HMG-CoA reductase in cholesterol synthesis, is reduced by degradation of SQLE upon elevation of cellular plasmalogen level. By contrast, the defect of plasmalogen synthesis causes elevation of SQLE expression, resulting in the reduction of 2,3-epoxysqualene required for cholesterol synthesis, hence implying a novel physiological consequence of the regulation of plasmalogen biosynthesis.
authors.affiliation: From the Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Honsho
authors.affiliation: From the Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Abe
authors.affiliation: From the Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan yfujiki@kyudai.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiki
mesh_terms: D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000096:biosynthesis* / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010955:Plasmalogens / Q000096:biosynthesis* / Q000235:genetics; D017368:Protein Prenylation / Q000502:physiology; D050603:Squalene Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D010955:Plasmalogens; C087343:PEX19 protein, human; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D050603:Squalene Monooxygenase; D020691:rab GTP-Binding Proteins
keywords: cell metabolism; cholesterol; endoplasmic reticulum (ER); peroxisome; plasmalogen; squalen; squalene monooxygenase