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101.
We make use of the yeast Saccharomyces cerevisiae as a flexible experimental system to investigate coordinate pathways of neutral lipid synthesis, storage and mobilization with special emphasis on the role of different organelles in these processes. Recently, a number of new gene products involved in triacylglycerol (TAG) and steryl ester (STE) metabolism were identified in our laboratory and by other groups. STE are synthesized by the two STE synthases Are1p and Are2p, whereas TAG are formed mainly through the action of the two TAG synthases Dga1p and Lro1p with minor contributions of Are1p and Are2p. Once formed, TAG and STE are stored in so-called lipid particles. A dga1Deltalro1Deltaare1Deltaare2Delta quadruple mutant which lacks neutral lipid synthesis and is consequently devoid of lipid particles turned out to be a valuable tool for studying the physiological role of storage lipids and lipid particles. Mobilization of neutral lipid depots occurs through catalysis of TAG lipases and STE hydrolases. Three TAG lipases named Tgl3p, Tgl4p and Tgl5p, and three STE hydrolases named Tgl1p, Yeh1p and Yeh2p were recently identified at the molecular level. Although these hydrolases exhibit overlapping function within the enzyme families, they are specific for TAG and STE, respectively. With the exception of Dga1p, whose activity is partially localized to lipid particles, TAG and STE forming enzymes are restricted to the endoplasmic reticulum. TAG lipases and STE hydrolases are components of lipid particles with the exception of Yeh2p, which is plasma membrane located. Thus, neutral lipid metabolism is not only regulated at the enzyme level but also by the distribution of the components to organelles. The fact that neutral lipid homeostasis is linked to a number of cell biological processes confirms the important role of this class of lipids as cellular modulators or effectors. 相似文献
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Martina Gsell Gerald Mascher Irmgard Schuiki Birgit Ploier Claudia Hrastnik Günther Daum 《PloS one》2013,8(10)
In the yeast, Saccharomyces cerevisiae, the synthesis of the essential phospholipid phosphatidylethanolamine (PE) is accomplished by a network of reactions which comprises four different pathways. The enzyme contributing most to PE formation is the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) which catalyzes conversion of phosphatidylserine (PS) to PE. To study the genome wide effect of an unbalanced cellular and mitochondrial PE level and in particular the contribution of Psd1p to this depletion we performed a DNA microarray analysis with a ∆psd1 deletion mutant. This approach revealed that 54 yeast genes were significantly up-regulated in the absence of PSD1 compared to wild type. Surprisingly, marked down-regulation of genes was not observed. A number of different cellular processes in different subcellular compartments were affected in a ∆psd1 mutant. Deletion mutants bearing defects in all 54 candidate genes, respectively, were analyzed for their growth phenotype and their phospholipid profile. Only three mutants, namely ∆gpm2, ∆gph1 and ∆rsb1, were affected in one of these parameters. The possible link of these mutations to PE deficiency and PSD1 deletion is discussed. 相似文献
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Diana Brust Bertram Daum Christine Breunig Andrea Hamann Werner Kühlbrandt Heinz D. Osiewacz 《Aging cell》2010,9(5):761-775
Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl‐cis,trans‐isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild‐type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild‐type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging. 相似文献
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Osama Odat Jason Gardiner Megan G. Sawchuk Carla Verna Tyler J. Donner Enrico Scarpella 《Genesis (New York, N.Y. : 2000)》2014,52(2):127-133
Patterning of numerous features of plants depends on transduction of the auxin signal. Auxin signaling is mediated by several pathways, the best understood of which relies on the function of the MONOPTEROS (MP) gene. Seven mp mutant alleles have been described in the widely used Columbia background of Arabidopsis: two extensively characterized and five only partially characterized. One of these five mp alleles appears to be extinct and thus unavailable for analysis. We show that two of the four remaining, partially characterized mp alleles reported to be in the Columbia background are in fact not in this background. We extend characterization of the remaining two Columbia alleles of mp, and we identify and characterize four new alleles of mp in the Columbia background, among which the first low‐expression allele of mp and the strongest Columbia allele of mp. These genetic resources provide the research community with new experimental opportunities for insight into the function of MP‐dependent auxin signaling in plant development. genesis 52:127–133. © 2013 Wiley Periodicals, Inc. 相似文献
107.
Utilization of exogenous glycerophosphodiesters and glycerol 3-phosphate by inositol-starved yeast, Saccharomyces uvarum 总被引:1,自引:0,他引:1
Inositol-starved Saccharomyces uvarum cells hydrolyse exogenous glycerophosphodiesters to glycerol 3-phosphate and the corresponding alcohol. Glycerophosphodiesterase activity is highest with glycerophosphoinositol as the substrate, followed by glycerophosphoethanolamine and glycerophosphocholine; the artificial substrate for phosphodiesterases, bis-p-nitrophenylphosphate,is hydrolysed at a similar rate as compared with glycerophosphoinositol. Competition experiments suggest that distinct phosphodiesterases are involved in the hydrolysis of the respective substrates. An Mg2+-dependent glycerophosphate phosphohydrolase with a pH-optimum around neutral cleaves glycerol 3-phosphate to glycerol and orthophosphate. The latter is taken up into cells without first entering the pool of orthophosphate present in the growth medium. Accessibility to substrates with whole cells, adhesion of enzymes to spheroplasts, and solubilization of enzymes by treatment of whole cells with Triton X-100 under mild conditions suggest that phosphodiesterases and glycerol-3-phosphate phosphohydrolase are loosely associated with the outer side of the yeast plasma membrane. Enzyme activities are only marginal in inositol-supplemented cells, but are derepressed not only by inositol deficiency, but also by starvation of orthophosphate. 相似文献
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