New perspectives on the regulation of intermembrane glycerophospholipid traffic

Voelker, Dennis R.

doi:10.1194/jlr.r200020-jlr200

Cited by 92 publications

(80 citation statements)

References 70 publications

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“…It has been known for some time that the ER and mitochondria are physically associated through specialized regions called mitochondrion-associated ER membranes (MAMs). Lipids, ATP, and calcium have been shown to exchange between the ER and the mitochondria through MAMs (49,65,73). Mitochondria also play a key role in phospholipid synthesis and transport (73).…”

Section: Discussionmentioning

confidence: 99%

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Wang

Deschenes

2006

Molecular and Cellular Biology

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Ras proteins are synthesized as cytosolic precursors, but then undergo posttranslational lipid addition, membrane association, and subcellular targeting to the plasma membrane. Although the enzymes responsible for farnesyl and palmitoyl lipid addition have been described, the mechanism by which these modifications contribute to the subcellular localization of Ras is not known. Following addition of the farnesyl group, Ras associates with the endoplasmic reticulum (ER), where palmitoylation occurs in Saccharomyces cerevisiae. The subsequent translocation of Ras from the ER to the plasma membrane does not require the classical secretory pathway or a functional Golgi apparatus. Vesicular and nonvesicular transport pathways for Ras proteins have been proposed, but the pathway is not known. Here we describe a genetic screen designed to identify mutants defective in Ras trafficking in S. cerevisiae. The screen implicates, for the first time, the class C VPS complex in Ras trafficking. Vps proteins are best characterized for their role in endosome and vacuole membrane fusion. However, the role of the class C Vps complex in Ras trafficking is distinct from its role in endosome and vacuole vesicle fusion, as a mitochondrial involvement was uncovered. Disruption of class C VPS genes results in mitochondrial defects and an accumulation of Ras proteins on mitochondrial membranes. Ras also fractionates with mitochondria in wild-type cells, where it is detected on the outer mitochondrial membrane by virtue of its sensitivity to protease treatment. These results point to a previously uncharacterized role of mitochondria in the subcellular trafficking of Ras proteins.

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Section: Discussionmentioning

confidence: 99%

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Wang

Deschenes

2006

Molecular and Cellular Biology

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“…Interestingly, peptides that mimic the α-helices of transmembrane proteins can stimulate phospholipid flip-flop in liposomes [18]. Enhanced flippase-type transfers are also necessary at membrane contact sites where lipids should be transferred from the cytosolic leaflet of the donor membrane to the cytosolic leaflet of the acceptor membrane [19]. It is possible that such flippases are involved in the transfer of DGDG from chloroplasts to mitochondria during phosphate deprivation since this transfer seems related to membrane contact [9 and see below].…”

Section: Energy-independent Flippasesmentioning

confidence: 99%

“…At a membrane contact site, membranes are typically separated by less than 10 nm [10]. The best-characterized membrane contact site was described in yeast between ER and mitochondria [19] during a study of the mechanisms for PE biosynthesis in mitochondria [80].…”

Section: Membrane Contact Sitesmentioning

confidence: 99%

“…The PS transfer from ER to the mitochondria outer membrane is not completely characterized. Data indicate ATP dependence of PS transfer, Ca2+ and Mg2+ stimulation, participation of a S100B protein (Ca2+-modulated protein of the EF-hand type) that binds calcium and can interact with annexin, and existence of a regulatory system involving a SCF (Skp1/Cul1/F-box protein) ubiquitin ligase [19]. PS is finally transported to the mitochondria inner membrane by an unknown mechanism, maybe going through contact sites between the inner and outer membranes of mitochondria [81].…”

Section: Pe Biosynthesis In Mitochondria Occurs By Decarboxylation Ofmentioning

confidence: 99%

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Glycerolipid transfer for the building of membranes in plant cells

Jouhet

Maréchal

Block

2007

Progress in Lipid Research

134

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“…In the model eukaryote Saccharomyces cerevisiae, PC is synthesized by complementary pathways that are common to those found in mammalian cells 2 ( Fig. 1) (1,4,(13)(14)(15)(16)(17). In the CDP-DAG pathway, PC is synthesized from CDP-DAG via the reactions catalyzed by PS synthase (18 -20), PS decarboxylase (21-23), PE methyltransferase (24, 25), and phospholipid methyltransferase (24,26).…”

mentioning

confidence: 99%

Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway

Choi

Sreenivas

Han

et al. 2004

Journal of Biological Chemistry

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In the yeast Saccharomyces cerevisiae, the most abundant phospholipid phosphatidylcholine is synthesized by the complementary CDP-diacylglycerol and Kennedy pathways. Using a cki1⌬ eki1⌬ mutant defective in choline kinase and ethanolamine kinase, we examined the consequences of a block in the Kennedy pathway on the regulation of phosphatidylcholine synthesis by the CDP-diacylglycerol pathway. The cki1⌬ eki1⌬ mutant exhibited increases in the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine via the CDP-diacylglycerol pathway. The increase in phospholipid synthesis correlated with increased activity levels of the CDPdiacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. However, other enzyme activities, including phosphatidylinositol synthase and phosphatidate phosphatase, were not affected in the cki1⌬ eki1⌬ mutant. For phosphatidylserine synthase, the enzyme catalyzing the committed step in the pathway, activity was regulated by increases in the levels of mRNA and protein. Decay analysis of CHO1 mRNA indicated that a dramatic increase in transcript stability was a major component responsible for the elevated level of phosphatidylserine synthase. These results revealed a novel mechanism that controls phospholipid synthesis in yeast.PC 1 is the most abundant phospholipid in the membranes of eukaryotic cells (1-4). It serves as a structural component of the membrane and as a source of bioactive lipids (e.g. lyso-PC, PA, DAG) (1-5). The importance of PC is underscored by the fact that alterations in its metabolism are linked to apoptosis (6 -9) and oncogenic transformation (10 -12). In the model eukaryote Saccharomyces cerevisiae, PC is synthesized by complementary pathways that are common to those found in mammalian cells 2 ( Fig. 1) (1,4,(13)(14)(15)(16)(17). In the CDP-DAG pathway, PC is synthesized from CDP-DAG via the reactions catalyzed by PS synthase (18 -20), PS decarboxylase (21-23), PE methyltransferase (24, 25), and phospholipid methyltransferase (24,26). In the CDP-choline branch of the Kennedy pathway, PC is synthesized from choline via the reactions catalyzed by choline kinase (27), phosphocholine cytidylyltransferase (28), and choline phosphotransferase (29,30). Analyses of mutations in S. cerevisiae (4, 31, 32), as well as in mammalian cells (33,34) indicate that the physiological role(s) of PC synthesized by the two pathways are different.The contribution of the CDP-DAG and Kennedy pathways for PC synthesis in wild type S. cerevisiae is dependent on the exogenous supply of choline (35). When grown in the presence of choline, yeast primarily synthesizes PC via the Kennedy pathway (35). On the other hand, when cells are grown in the absence of choline, PC is primarily synthesized via the CDP-DAG pathway (35). Yet, even under this growth condition, the Kennedy pathway still contributes to the synthesis of PC (36 -41). The choline required for the Kenne...

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New perspectives on the regulation of intermembrane glycerophospholipid traffic

Cited by 92 publications

References 70 publications

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Glycerolipid transfer for the building of membranes in plant cells

Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway

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