Limits...
The emergence of lipid droplets in yeast: current status and experimental approaches.

Radulovic M, Knittelfelder O, Cristobal-Sarramian A, Kolb D, Wolinski H, Kohlwein SD - Curr. Genet. (2013)

Bottom Line: The previous view of a rather inert storage pool of neutral lipids--triacylglycerol and sterols or steryl esters--has markedly changed.Driven by the endemic dimensions of lipid-associated disorders on the one hand, and the promising biotechnological application to generate oils ('biodiesel') from single-celled organisms on the other, multiple model organisms are exploited in basic and applied research to develop a better understanding of biogenesis and metabolism of this organelle.This article summarizes the current status of LD research in yeast and experimental approaches to obtain insight into the regulatory and structural components driving lipid droplet formation and their physiological and pathophysiological roles in lipid homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010, Graz, Austria.

ABSTRACT
The 'discovery' of lipid droplets as a metabolically highly active subcellular organelle has sparked great scientific interest in its research in recent years. The previous view of a rather inert storage pool of neutral lipids--triacylglycerol and sterols or steryl esters--has markedly changed. Driven by the endemic dimensions of lipid-associated disorders on the one hand, and the promising biotechnological application to generate oils ('biodiesel') from single-celled organisms on the other, multiple model organisms are exploited in basic and applied research to develop a better understanding of biogenesis and metabolism of this organelle. This article summarizes the current status of LD research in yeast and experimental approaches to obtain insight into the regulatory and structural components driving lipid droplet formation and their physiological and pathophysiological roles in lipid homeostasis.

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Pathways of neutral lipid metabolism in yeast (Henry et al. 2012; Kohlwein et al. 2013). Red areas mark lipid droplets. Whether steryl ester and triacylglycerol form distinct or mixed LDs is currently unknown. The mechanisms by which TAGs (that are mostly) and SE (that are exclusively) generated in the ER enter the LD are unknown. It is also unclear whether and to what extent DAG derived form lipolysis is directly utilized for re-acylation or for phospholipid synthesis; the stereochemistry of the lipolysis reaction in yeast has not yet been worked out. Gro glycerol, DHAP dihydroxyacetone phosphate, Gro-3P glycerol-3-phosphate, Lyso-PA sn1-acyl-gycerol-3-phosphate (lyso phosphatidic acid), PA phosphatidic acid, DAG diacylgycerol, MAG monoacylglycerol, SE steryl esters, FFA free fatty acids, FS free sterol, ER endoplasmic reticulum, PM plasma membrane. (See text for details)
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Fig2: Pathways of neutral lipid metabolism in yeast (Henry et al. 2012; Kohlwein et al. 2013). Red areas mark lipid droplets. Whether steryl ester and triacylglycerol form distinct or mixed LDs is currently unknown. The mechanisms by which TAGs (that are mostly) and SE (that are exclusively) generated in the ER enter the LD are unknown. It is also unclear whether and to what extent DAG derived form lipolysis is directly utilized for re-acylation or for phospholipid synthesis; the stereochemistry of the lipolysis reaction in yeast has not yet been worked out. Gro glycerol, DHAP dihydroxyacetone phosphate, Gro-3P glycerol-3-phosphate, Lyso-PA sn1-acyl-gycerol-3-phosphate (lyso phosphatidic acid), PA phosphatidic acid, DAG diacylgycerol, MAG monoacylglycerol, SE steryl esters, FFA free fatty acids, FS free sterol, ER endoplasmic reticulum, PM plasma membrane. (See text for details)

Mentions: The enzymology of (neutral) lipid synthesis has been very well worked out in the yeast S. cerevisiae [see (Henry et al. 2012; Kohlwein et al. 2013) for recent reviews]; however, the mechanisms involved in LD formation are currently unknown and several models have been put forward to explain the presence of a monolayer of phospholipids, which delineates the LD surface. All these models have in common that LDs are derived from the endoplasmic reticulum (ER), which harbors also most of the enzymes involved in the formation of the neutral lipid core (Kohlwein et al. 2013). Figure 2 summarizes the biochemical pathways associated with the formation of neutral lipids, triacylglycerol (TAG) and steryl esters (SE), which form the core of the LD. Thus, processes affecting neutral lipid homeostasis can be potentially identified by morphological alterations of lipid droplet structure(s); conversely, mechanisms driving LD formation likely also regulate the synthesis of LD lipids. Noteworthy, the initial pathway of TAG synthesis up to phosphatidic acid is shared with the biosynthesis of the ‘de novo’ branch of phospholipid synthesis, which leads to all major phospholipid classes under normal growth conditions (Henry et al. 2012). In addition, diacylglycerol, which is generated (among other pathways) by dephosphorylation of phosphatidic acid by the conserved enzyme phosphatidate phosphatase (Pah1 in yeast, Lipin in mammals), serves as a phospholipid precursor, by utilizing ethanolamine or choline precursors derived from exogenous sources or from internal phospholipid turnover to form phosphatidylethanolamine or phosphatidylcholine, respectively. Thus, it is not surprising that processes affecting TAG homeostasis also affect phospholipid metabolism and, as a consequence, membrane function. Conversely, defective phospholipid synthesis and turnover also trigger TAG accumulation (Gaspar et al. 2008; Malanovic et al. 2008). This close metabolic interrelationship between TAG synthesis and membrane lipid composition and function may be the underlying cause of lipotoxic cell damage, which further underscores the importance of obtaining a clearer picture of the mechanisms of TAG storage into LD.Fig. 2


The emergence of lipid droplets in yeast: current status and experimental approaches.

Radulovic M, Knittelfelder O, Cristobal-Sarramian A, Kolb D, Wolinski H, Kohlwein SD - Curr. Genet. (2013)

Pathways of neutral lipid metabolism in yeast (Henry et al. 2012; Kohlwein et al. 2013). Red areas mark lipid droplets. Whether steryl ester and triacylglycerol form distinct or mixed LDs is currently unknown. The mechanisms by which TAGs (that are mostly) and SE (that are exclusively) generated in the ER enter the LD are unknown. It is also unclear whether and to what extent DAG derived form lipolysis is directly utilized for re-acylation or for phospholipid synthesis; the stereochemistry of the lipolysis reaction in yeast has not yet been worked out. Gro glycerol, DHAP dihydroxyacetone phosphate, Gro-3P glycerol-3-phosphate, Lyso-PA sn1-acyl-gycerol-3-phosphate (lyso phosphatidic acid), PA phosphatidic acid, DAG diacylgycerol, MAG monoacylglycerol, SE steryl esters, FFA free fatty acids, FS free sterol, ER endoplasmic reticulum, PM plasma membrane. (See text for details)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Pathways of neutral lipid metabolism in yeast (Henry et al. 2012; Kohlwein et al. 2013). Red areas mark lipid droplets. Whether steryl ester and triacylglycerol form distinct or mixed LDs is currently unknown. The mechanisms by which TAGs (that are mostly) and SE (that are exclusively) generated in the ER enter the LD are unknown. It is also unclear whether and to what extent DAG derived form lipolysis is directly utilized for re-acylation or for phospholipid synthesis; the stereochemistry of the lipolysis reaction in yeast has not yet been worked out. Gro glycerol, DHAP dihydroxyacetone phosphate, Gro-3P glycerol-3-phosphate, Lyso-PA sn1-acyl-gycerol-3-phosphate (lyso phosphatidic acid), PA phosphatidic acid, DAG diacylgycerol, MAG monoacylglycerol, SE steryl esters, FFA free fatty acids, FS free sterol, ER endoplasmic reticulum, PM plasma membrane. (See text for details)
Mentions: The enzymology of (neutral) lipid synthesis has been very well worked out in the yeast S. cerevisiae [see (Henry et al. 2012; Kohlwein et al. 2013) for recent reviews]; however, the mechanisms involved in LD formation are currently unknown and several models have been put forward to explain the presence of a monolayer of phospholipids, which delineates the LD surface. All these models have in common that LDs are derived from the endoplasmic reticulum (ER), which harbors also most of the enzymes involved in the formation of the neutral lipid core (Kohlwein et al. 2013). Figure 2 summarizes the biochemical pathways associated with the formation of neutral lipids, triacylglycerol (TAG) and steryl esters (SE), which form the core of the LD. Thus, processes affecting neutral lipid homeostasis can be potentially identified by morphological alterations of lipid droplet structure(s); conversely, mechanisms driving LD formation likely also regulate the synthesis of LD lipids. Noteworthy, the initial pathway of TAG synthesis up to phosphatidic acid is shared with the biosynthesis of the ‘de novo’ branch of phospholipid synthesis, which leads to all major phospholipid classes under normal growth conditions (Henry et al. 2012). In addition, diacylglycerol, which is generated (among other pathways) by dephosphorylation of phosphatidic acid by the conserved enzyme phosphatidate phosphatase (Pah1 in yeast, Lipin in mammals), serves as a phospholipid precursor, by utilizing ethanolamine or choline precursors derived from exogenous sources or from internal phospholipid turnover to form phosphatidylethanolamine or phosphatidylcholine, respectively. Thus, it is not surprising that processes affecting TAG homeostasis also affect phospholipid metabolism and, as a consequence, membrane function. Conversely, defective phospholipid synthesis and turnover also trigger TAG accumulation (Gaspar et al. 2008; Malanovic et al. 2008). This close metabolic interrelationship between TAG synthesis and membrane lipid composition and function may be the underlying cause of lipotoxic cell damage, which further underscores the importance of obtaining a clearer picture of the mechanisms of TAG storage into LD.Fig. 2

Bottom Line: The previous view of a rather inert storage pool of neutral lipids--triacylglycerol and sterols or steryl esters--has markedly changed.Driven by the endemic dimensions of lipid-associated disorders on the one hand, and the promising biotechnological application to generate oils ('biodiesel') from single-celled organisms on the other, multiple model organisms are exploited in basic and applied research to develop a better understanding of biogenesis and metabolism of this organelle.This article summarizes the current status of LD research in yeast and experimental approaches to obtain insight into the regulatory and structural components driving lipid droplet formation and their physiological and pathophysiological roles in lipid homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010, Graz, Austria.

ABSTRACT
The 'discovery' of lipid droplets as a metabolically highly active subcellular organelle has sparked great scientific interest in its research in recent years. The previous view of a rather inert storage pool of neutral lipids--triacylglycerol and sterols or steryl esters--has markedly changed. Driven by the endemic dimensions of lipid-associated disorders on the one hand, and the promising biotechnological application to generate oils ('biodiesel') from single-celled organisms on the other, multiple model organisms are exploited in basic and applied research to develop a better understanding of biogenesis and metabolism of this organelle. This article summarizes the current status of LD research in yeast and experimental approaches to obtain insight into the regulatory and structural components driving lipid droplet formation and their physiological and pathophysiological roles in lipid homeostasis.

Show MeSH
Related in: MedlinePlus