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Changcheng Xu - One of the best experts on this subject based on the ideXlab platform.
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arabidopsis lipins pdat1 acyltransferase and sdp1 triacylglycerol lipase synergistically direct fatty acids toward β oxidation thereby maintaining membrane Lipid Homeostasis
The Plant Cell, 2014Co-Authors: Rebecca L Roston, John Shanklin, Changcheng XuAbstract:Triacylglycerol (TAG) metabolism is a key aspect of intracellular Lipid Homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLipid:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane Lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf Lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf Lipid, by 3-fold. The membrane Lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactoLipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane Lipid Homeostasis in leaves.
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arabidopsis lipins pdat1 acyltransferase and sdp1 triacylglycerol lipase synergistically direct fatty acids toward β oxidation thereby maintaining membrane Lipid Homeostasis
The Plant Cell, 2014Co-Authors: Rebecca L Roston, John Shanklin, Changcheng XuAbstract:Triacylglycerol (TAG) metabolism is a key aspect of intracellular Lipid Homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLipid:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane Lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf Lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf Lipid, by 3-fold. The membrane Lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactoLipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane Lipid Homeostasis in leaves.
Rebecca L Roston - One of the best experts on this subject based on the ideXlab platform.
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arabidopsis lipins pdat1 acyltransferase and sdp1 triacylglycerol lipase synergistically direct fatty acids toward β oxidation thereby maintaining membrane Lipid Homeostasis
The Plant Cell, 2014Co-Authors: Rebecca L Roston, John Shanklin, Changcheng XuAbstract:Triacylglycerol (TAG) metabolism is a key aspect of intracellular Lipid Homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLipid:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane Lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf Lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf Lipid, by 3-fold. The membrane Lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactoLipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane Lipid Homeostasis in leaves.
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arabidopsis lipins pdat1 acyltransferase and sdp1 triacylglycerol lipase synergistically direct fatty acids toward β oxidation thereby maintaining membrane Lipid Homeostasis
The Plant Cell, 2014Co-Authors: Rebecca L Roston, John Shanklin, Changcheng XuAbstract:Triacylglycerol (TAG) metabolism is a key aspect of intracellular Lipid Homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLipid:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane Lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf Lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf Lipid, by 3-fold. The membrane Lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactoLipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane Lipid Homeostasis in leaves.
John Shanklin - One of the best experts on this subject based on the ideXlab platform.
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arabidopsis lipins pdat1 acyltransferase and sdp1 triacylglycerol lipase synergistically direct fatty acids toward β oxidation thereby maintaining membrane Lipid Homeostasis
The Plant Cell, 2014Co-Authors: Rebecca L Roston, John Shanklin, Changcheng XuAbstract:Triacylglycerol (TAG) metabolism is a key aspect of intracellular Lipid Homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLipid:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane Lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf Lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf Lipid, by 3-fold. The membrane Lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactoLipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane Lipid Homeostasis in leaves.
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arabidopsis lipins pdat1 acyltransferase and sdp1 triacylglycerol lipase synergistically direct fatty acids toward β oxidation thereby maintaining membrane Lipid Homeostasis
The Plant Cell, 2014Co-Authors: Rebecca L Roston, John Shanklin, Changcheng XuAbstract:Triacylglycerol (TAG) metabolism is a key aspect of intracellular Lipid Homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLipid:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane Lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf Lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf Lipid, by 3-fold. The membrane Lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactoLipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane Lipid Homeostasis in leaves.
Tanja Fehm - One of the best experts on this subject based on the ideXlab platform.
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abstract p2 04 02 progesterone receptor membrane component 1 a novel key regulator in Lipid Homeostasis drives oncogenic signaling resulting in breast cancer progression
Cancer Research, 2020Co-Authors: H Asperger, Zaklina Kovacevic, Des R Richardson, Marina Ludescher, N Stamm, Janphilipp Cieslik, Ute Hofmann, Ulrich M Zanger, E Ruckhaberle, Tanja FehmAbstract:Background: PGRMC1 (progesterone receptor membrane component 1) is a highly conserved heme binding protein which is overexpressed especially in hormone receptor positive breast cancer and plays an important role in breast cancer carcinogenesis. Nevertheless, little is known about the mechanisms by which PGRMC1 drives tumor progression. Based on our previous studies on the involvement of PGRMC1 in cholesterol metabolism we describe a potential mechanism by which PGRMC1 can increase Lipid metabolism and alter EGFR signaling. Methods: To obtain PGRMC1 overexpressing cell lines, MCF7, T47D and MDA cells were stably transfected with expression plasmid pcDNA3.1. containing HA-tagged PGRMC1. As a control, cells transfected with the empty plasmid were used.To investigate the role of PGRMC1 in breast cancer progression, expression of genes involved in Lipid metabolism were quantified by qPCR. Subsequent Lipid and cholesterol levels as well as Lipid raft expression were measured by flow cytometry in various breast cancer cell lines overexpressing PGRMC1 compared to empty vector control. Since many studies show that EGFR is enriched in Lipid rafts, we further investigated alteration of EGFR/HER2 signaling through PGRMC1 overexpression via western blot and immunofluorescence analyses. The impact of Lipid inhibition on tumor progression was analyzed by viability assays. Results: PGRMC1 overexpression resulted in higher levels of mRNA coding for proteins responsible for Lipid Homeostasis (SREPF1, SREBF2), Lipid uptake (LDLR) and Lipid synthesis (FASN, HMGCS, SCD, ACAT) leading to higher levels of neutral Lipids, estradiol and cholesterol. Furthermore, PGRMC1 overexpressing hormone receptor positive cells show increased Lipid raft formation with higher expression of EGFR/HER2 and altered EGFR/HER2 signaling. PGRMC1 overexpressing cells are more sensitive to a simvastatin treatment, which indicates a higher dependence of PGRMC1 overexpressing cells on cholesterol synthesis. Conclusion: Cholesterol and Lipid metabolism play an important role in breast carcinogenesis. Our recent studies underline the effects of PGRMC1 on increasing Lipid synthesis and uptake thereby altering oncogenic signaling. PGRMC1 overexpressing breast cancer cells could be particularly suitable for a statin treatment. Citation Format: Hannah Asperger, Marina Ludescher, Nadia Stamm, Jan-Philipp Cieslik, Ute Hofmann, Ulrich Zanger, Zaklina Kovacevic, Des Richardson, Eugen Ruckhaberle, Tanja Fehm, Dieter Niederacher, Hans Neubauer. Progesterone receptor membrane component 1 - A novel key regulator in Lipid Homeostasis drives oncogenic signaling resulting in breast cancer progression [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-04-02.
Janelle E Collinge - One of the best experts on this subject based on the ideXlab platform.
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A Mouse Model of Harlequin Ichthyosis Delineates a Key Role for Abca12 in Lipid Homeostasis
2013Co-Authors: Ian Smyth, Douglas F Hacking, Nigora Mukhamedova, Keith Slattery, Janelle E Collinge, Adrienne A Hilton, Peter J. Meikle, Sarah Ellis, Carolyn A. De Graaf, Melanie BahloAbstract:Harlequin Ichthyosis (HI) is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of Lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in Lipid Homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of Lipid levels in mutant epidermis demonstrated profound defects in Lipid Homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining Lipid balance in the skin. To further investigate the scope of Abca12’s activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired Lipid efflux leading t
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a mouse model of harlequin ichthyosis delineates a key role for abca12 in Lipid Homeostasis
PLOS Genetics, 2008Co-Authors: Ian M Smyth, Douglas F Hacking, Nigora Mukhamedova, Sarah Reichardt Ellis, Keith Slattery, Janelle E Collinge, Adrienne A Hilton, Peter J. MeikleAbstract:Harlequin Ichthyosis (HI) is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of Lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in Lipid Homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of Lipid levels in mutant epidermis demonstrated profound defects in Lipid Homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining Lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired Lipid efflux leading to intracellular accumulation of neutral Lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of Lipid metabolism and Homeostasis, including atherosclerosis.