Topogenesis and Homeostasis of Fatty Acyl-CoA Reductase 1

Honsho, Masanori; Asaoku, Shunsuke; Fukumoto, Keiko; Fujiki, Yukio

doi:10.1074/jbc.m113.498345

Cited by 61 publications

(87 citation statements)

References 43 publications

(21 reference statements)

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“…2C). Elevation of plasmalogens in CHO-K1 cells were performed as described (6,7). To increase cellular cholesterol, cells were cultured in the presence of 20 g/ml of cholesterol complexed with methyl-␤-cyclodextrin (15) for 16 h (12) or the indicated time.…”

Section: Methodsmentioning

confidence: 99%

“…Plasmalogens and phosphatidylethanolamine were analyzed by TLC (6,7,13) or LC-ESI-MS/MS (17). Cellular free cholesterol was determined by the enzymatic method using an Amplex Red cholesterol assay kit according to the manufacturer's instruction (Molecular Probes).…”

Section: Methodsmentioning

confidence: 99%

“…This fatty alcohol is generated by a peroxisomal C-tail anchored protein, fatty acyl-CoA reducatase 1 (Far1) (5,6). We earlier demonstrated that Far1 activity is regulated by modulating its stability in response to the cellular level of plasmalogens (6,7). Very recently, a plasmalogen-deficient disorder with intellectual disability, epilepsy, and cataracts was shown in a FAR1-defective patient, implying the essential function of Far1 in plasmalogen synthesis (8).…”

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confidence: 99%

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Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis

Honsho

Abe

Fujiki

2015

Journal of Biological Chemistry

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Background: Physiological significance of plasmalogen homeostasis remains unknown. Results: Elevation of plasmalogens reduced cholesterol synthesis by enhancing degradation of squalene monooxygenase (SQLE), whereas SQLE was stabilized in the absence of plasmalogens. Conclusion: Plasmalogens regulate cholesterol synthesis by modulating the stability of SQLE. Significance: SQLE stability is modulated in response to the cellular level of plasmalogens, in addition to the acute changes of cholesterol level.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis

Honsho

Abe

Fujiki

2015

Journal of Biological Chemistry

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“…The decreased expression of FAR1 in HepG2 cells treated with C18:1 and C22:1 may have resulted from the negative feedback from the overproduction of Pls. MI is presumed to enhance Pl biosynthesis through NADPH generation during MI catabolism [31], since Far 1 is activated via NADPH binding [32]. Therefore, the suppressed expression of Pl biosynthetic enzymes in cells treated with MI could also be caused by the negative feedback from overproduction of Pl.…”

Section: Discussionmentioning

confidence: 99%

Extrinsic effectors regulating genes for plasmalogen biosynthetic enzymes in HepG2 cells

Maeba¹,

Nakahara²

2017

Biomed Res Clin Prac

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Plasma plasmalogens (Pls) may serve as potential biomarkers not only for rare peroxisomal diseases but also for general disorders related to oxidative stress and aging. Recent clinical observational studies demonstrated that low levels of plasma Pls are risk factors for atherosclerosis and dementia. Serum levels of Pls showed a strong positive correlation with high-density lipoprotein (HDL) cholesterol concentration, suggesting that Pls may be involved in metabolism or the function of HDL. Increasing the levels of plasma Pls may serve as a novel therapeutic strategy for preventing diseases associated with oxidative stress and aging. Therefore, we and other groups elevated plasma Pl levels in laboratory animals or humans through administration of myo-inositol, monounsaturated long-chain fatty acids, and the hypolipidemic agent, statin. However, their effects on the gene expression of Pl biosynthetic enzymes remain unknown. To gain insight into the manipulation of Pl biosynthesis and the relationship between Pl biosynthesis and HDL metabolism, we examined target gene expression by real time reverse transcription polymerase chain reaction (RT-PCR) in hepatoma HepG2 cells treated with various test substances. Monounsaturated long-chain fatty acids such as oleic acid and erucic acid, myo-inositol, and the Pl precursor alkylglycerol, all of which supply materials or coenzymes for Pl biosynthesis, unexpectedly reduced the expression of the genes for Pl biosynthetic enzymes. These results suggest the presence of strict regulation of Pl homeostasis. In contrast, pitavastatin induced peroxisome biogenesis and promoted the expression of peroxisomal Pl biosynthetic enzymes and HDL metabolism-associated proteins such as apoprotein A1 and ATP-binding cassette transporter A1. This was likely through enhancement of peroxisome proliferator-activated receptor (PPAR) expression. These findings suggest that there may be a physiological relationship between Pl biosynthesis and HDL metabolism via peroxisomal status.

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“…Importantly, this acyl-CoA reductase activity was found at the outer aspect of the peroxisomal membrane, which implies that the substrates including the acyl-CoA ester plus NADPH are in the cytosol and not localized in the peroxisomal matrix (see Figure 2). Most likely, the long-chain alcohol produced in the acyl-CoA reductase reaction is also released at the cytosolic face of the peroxisomal membrane (see Figure 2B; Honsho et al, 2013).…”

Section: (A) Etherphospholipid Biosynthesismentioning

confidence: 99%

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

2017

Frontiers Research Topics

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Topogenesis and Homeostasis of Fatty Acyl-CoA Reductase 1

Cited by 61 publications

References 43 publications

Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis

Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis

Extrinsic effectors regulating genes for plasmalogen biosynthetic enzymes in HepG2 cells

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

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