Heterogeneous Distribution of the Unusual Phospholipid Semilysobisphosphatidic Acid through the Golgi Complex

Cluett, Edward B.; Kuismanen, Esa; Machamer, Carolyn E.

doi:10.1091/mbc.8.11.2233

Cited by 44 publications

(42 citation statements)

References 48 publications

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“…A few PE (three lipids), PI (three lipids), PS (two lipids), and a PA (one lipid) were also observed. Acyl-PG are unusual lipids commonly found in bacterial cells, which have been reported to accumulate in mitochrondrial fractions of mammalian apoptotic cells (31), and to be present at significant levels in Golgi membranes (32). PG lipids are present at low levels (1-2%) in most animal tissue and can serve as the precursor of CL found in mitochrondrial membranes.…”

Section: Resultsmentioning

confidence: 99%

Alteration of the lipid profile in lymphomas induced by MYC overexpression

Eberlin

Gabay

Fan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

120

103

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Overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC) oncogene is one of the most commonly implicated causes of human tumorigenesis. MYC is known to regulate many aspects of cellular biology including glucose and glutamine metabolism. Little is known about the relationship between MYC and the appearance and disappearance of specific lipid species. We use desorption electrospray ionization mass spectrometry imaging (DESI-MSI), statistical analysis, and conditional transgenic animal models and cell samples to investigate changes in lipid profiles in MYC-induced lymphoma. We have detected a lipid signature distinct from that observed in normal tissue and in rat sarcoma-induced lymphoma cells. We found 104 distinct molecular ions that have an altered abundance in MYC lymphoma compared with normal control tissue by statistical analysis with a false discovery rate of less than 5%. Of these, 86 molecular ions were specifically identified as complex phospholipids. To evaluate whether the lipid signature could also be observed in human tissue, we examined 15 human lymphoma samples with varying expression levels of MYC oncoprotein. Distinct lipid profiles in lymphomas with high and low MYC expression were observed, including many of the lipid species identified as significant for MYC-induced animal lymphoma tissue. Our results suggest a relationship between the appearance of specific lipid species and the overexpression of MYC in lymphomas.biostatistics | transgenic models | lipidomics | metabolomics | cancer T he v-myc avian myelocytomatosis viral oncogene homolog (MYC) is commonly overexpressed in human neoplasia (1, 2) and has been strongly associated with the clinical aggressiveness of human cancers (3, 4). MYC is particularly associated with the pathogenesis of hematopoietic tumors such as lymphomas and of epithelial tumors (5, 6). In Burkitt's lymphoma, for example, the c-Myc gene is translocated to one of the Ig loci in virtually all tumors (5,7,8). The MYC oncogene contributes to tumorigenesis by functioning as a global regulator of transcription involving many cellular programs, including cellular growth, metabolism, and lipid synthesis (9, 10). MYC induces a global shift in metabolism associated with anaerobic glycolysis, a phenomenon known as the Warburg effect (11). Several studies have shown a relationship between MYC regulation and metabolism in lymphomas, especially as related to the processes of glycolysis and glutaminolysis (12, 13). Some reports suggest that MYC regulates fatty acid synthesis, specifically palmitate (14); however, little is known about the relationship between MYC expression and the up-regulation or down-regulation of various lipid species in lymphomas.We have generated transgenic mice to conditionally regulate expression of MYC oncogenes alone or in combination with oncogenes such as rat sarcoma (RAS), BCR-ABL, and BCL2 to produce many transgenic models of cancers, including T-cell acute lymphocytic leukemia, acute myeloid leukemia, osteosarcoma, lung adenocarc...

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Section: Resultsmentioning

confidence: 99%

Alteration of the lipid profile in lymphomas induced by MYC overexpression

Eberlin

Gabay

Fan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

120

103

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“…Stock solutions of cyclodextrins were freshly prepared at 50 mM in water. [3,[4][5][6][7][8][9][10][11][12][13] C 2 ]Cholesterol was kindly provided by Dr. Wolfgang D. Lehmann (German Cancer Research Center, Germany). 2,2,3,4,4,6-D 6 -cholesterol was purchased from Cambridge Isotope Laboratories, Inc. (Andover, MA).…”

Section: Methodsmentioning

confidence: 99%

“…The pellet was resuspended in the original volume with 1,4-dioxane. For quantitation, an internal standard was added to the samples, and after sulfatation of the cholesterol, cholesterol was measured with ESI-MS/MS by scanning in the negative mode for the parent ions of m/z ϭ 97 (HSO 4 Ϫ ) or 80 (SO 3 Ϫ ), depending on the internal standard ( [3,[4][5][6][7][8][9][10][11][12][13] C 2 ]cholesterol and 2,2,3,4,4,6-D 6 -cholesterol, respectively). Phosphatidylcholine, sphingomyelin, and glucosylceramide analysis by ESI-MS/MS was performed as described previously (36).…”

Section: Methodsmentioning

confidence: 99%

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Stüven

Porat

Shimron

et al. 2003

Journal of Biological Chemistry

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Transport of proteins between intracellular membrane compartments is mediated by a protein machinery that regulates the budding and fusion processes of individual transport steps. Although the core proteins of both processes are defined at great detail, much less is known about the involvement of lipids. Here we report that changing the cellular balance of cholesterol resulted in changes of the morphology of the Golgi apparatus, accompanied by an inhibition of protein transport. By using a well characterized cell-free intra-Golgi transport assay, these observations were further investigated, and it was found that the transport reaction is sensitive to small changes in the cholesterol content of Golgi membranes. Addition as well as removal of cholesterol (10 ؎ 6%) to Golgi membranes by use of methyl-␤-cyclodextrin specifically inhibited the intra-Golgi transport assay. Transport inhibition occurred at the fusion step. Modulation of the cholesterol content changed the lipid raft partitioning of phosphatidylcholine and heterotrimeric G proteins, but not of other (non) lipid raft proteins and lipids. We suggest that the cholesterol balance in Golgi membranes plays an essential role in intra-Golgi protein transport and needs to be carefully regulated to maintain the structural and functional organization of the Golgi apparatus.

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“…Unsaturated fatty acids block HIV budding [126] Mycobactin mediates iron supply within macrophages [32] FA Affinity of HIV Gag protein is regulated by myristoyl switch [127] Presentation of glycerophospholipids, sulfolipids and mycolates via CD1 receptors [58,132,133] GP Golgi-derived viruses have different phospholipid (incl semilysobisphosphatidic acid) composition depending on the precise site of budding [7,128] HIV-like particle assembly is regulated by inositol phosphates [129] HIV-1 Gag targeting is regulated by PIP2 [130] Vaccinia virus envelope protein p37 has lipase activity [131] Nef transports cholesterol to site of HIV budding [134] ST Budding occurs from glycolipid-enriched membrane lipid rafts [8,[135][136][137] Table summarizing the reported involvement of lipids, both from the host as well as the pathogen, during various stages of host-pathogen interaction ( Fig. 1).…”

Section: Glmentioning

confidence: 99%

Lipidomics of host–pathogen interactions

Wenk

2006

FEBS Letters

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The cell biology of intracellular pathogens (viruses, bacteria, eukaryotic parasites) has provided us with molecular information of host-pathogen interactions. As a result it is becoming increasingly evident that lipids play important roles at various stages of host-pathogen interactions. They act in first line recognition and host cell signaling during pathogen docking, invasion and intracellular trafficking. Lipid metabolism is a housekeeping function in energy homeostasis and biomembrane synthesis during pathogen replication and persistence. Lipids of enormous chemical diversity play roles as immunomodulatory factors. Thus, novel biochemical analytics in combination with cell and molecular biology are a promising recipe for dissecting the roles of lipids in host-pathogen interactions.

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Heterogeneous Distribution of the Unusual Phospholipid Semilysobisphosphatidic Acid through the Golgi Complex

Cited by 44 publications

References 48 publications

Alteration of the lipid profile in lymphomas induced by MYC overexpression

Alteration of the lipid profile in lymphomas induced by MYC overexpression

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Lipidomics of host–pathogen interactions

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