Functions and biosynthesis of plasmalogens in health and disease

Brites, Pedro; Waterham, Hans R.; Wanders, Ronald J. A.

doi:10.1016/j.bbalip.2003.12.010

Cited by 357 publications

(351 citation statements)

References 132 publications

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“…Interestingly, in light of the multivariate analyses performed here, it can be concluded that subtle changes observed in the plasmalogens (that is, 18:0 DMA) and cerebroside contents are sufficient to discriminate between PD and iPD lipid rafts. Moreover, it was suggested that plasmalogens can act as storage depots of DHA and AA given their high levels in plasmalogens when compared with their diacyl counterparts (34,35). In agreement, we could demonstrate that the impoverishment of plasmalogens correlates with that of AA (and DHA) in PD and iPD lipid rafts.…”

Section: Discussionsupporting

confidence: 77%

“…One interesting property of plasmalogens is that they have the ability to form nonlamellar structures and can allow the transition of membranes from a lamellar gel to liquid-crystalline form. Obviously, these physical properties contribute to, or modulate, the formation and/or maintenance of lipid rafts (34). On the basis of these assumptions, the considerable reduction of plasmalogen levels in PD strongly indicates altered physicochemical properties and protein-lipid dynamics within frontal cortex lipid rafts in PD neuropathology.…”

Section: Discussionmentioning

confidence: 99%

“…These ether fatty acids are formed exclusively from neutral plasmalogens upon acidic transesterification methods used to prepare fatty acid methyl esters (as used here). In the plasmalogen molecule, the aliphatic moieties at the sn-1 position consist of C18:0 (and to a lesser extent, C16:0 and C18:1-n9) carbon chains forming a vinyl-ether bond, whereas the sn-2 position is occupied by PUFAs, specifically AA or DHA (33,34). Therefore, the amount of DMA fatty acids stoichiometrically reflects that of plasmalogens, being commonly used as a quantitative measure of total plasmalogens, mainly represented by the PE class (plasmenylethanolamines) with rather less in PC, and commonly little or none in other phospholipids such as PI (33,35).…”

Section: S E P T E M B E R -O C T O B E R 2 0 1 1 L I P I D R a F Tmentioning

confidence: 99%

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Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

Fabelo

Martín

Santpere

et al. 2011

Mol Med

317

253

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Lipid rafts are cholesterol-and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein-lipid and protein-protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson's disease (PD) and incidental Parkinson's disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: S E P T E M B E R -O C T O B E R 2 0 1 1 L I P I D R a F Tmentioning

confidence: 99%

See 1 more Smart Citation

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

Fabelo

Martín

Santpere

et al. 2011

Mol Med

317

253

View full text Add to dashboard Cite

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“…This compartmentalization is essential for the survival of the blood-stream form of African trypanosomes and is therefore an attractive target for drug therapies (Moyersoen et al, 2004). In mammals, peroxisomes are responsible for key enzymatic steps in the synthesis of plasmalogens -ether-linked phospholipids that are abundant in brain and nervous tissue (Brites et al, 2004). Peroxisomes of fungi often contain environmentally inducible enzymes, for example, those involved in metabolism of methanol (van der Klei et al, 2006) or biosynthesis of penicillin (van den .…”

Section: Introductionmentioning

confidence: 99%

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

Lanyon‐Hogg

Warriner

Baker

2010

Biology of the Cell

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Peroxisomes are a family of organelles which have many unusual features. They can arise de novo from the endoplasmic reticulum by a still poorly characterized process, yet possess a unique machinery for the import of their matrix proteins. As peroxisomes lack DNA, their function, which is highly variable and dependent on developmental and/or environmental conditions, is determined by the post-translational import of specific metabolic enzymes in folded or oligomeric states. The two classes of matrix targeting signals for peroxisomal proteins [PTS1 (peroxisomal targeting signal 1) and PTS2] are recognized by cytosolic receptors [PEX5 (peroxin 5) and PEX7 respectively] which escort their cargo proteins to, or possibly across, the peroxisome membrane. Although the membrane translocation mechanism remains unclear, it appears to be driven by thermodynamically favourable binding interactions. Recycling of the receptors from the peroxisome membrane requires ATP hydrolysis for two linked processes: ubiquitination of PEX5 (and the PEX7 co-receptors in yeast) and the function of two peroxisome-associated AAA (ATPase associated with various cellular activities) ATPases, which play a role in recycling or turnover of the ubiquitinated receptors. This review summarizes and integrates recent findings on peroxisome matrix protein import from yeast, plant and mammalian model systems, and discusses some of the gaps in our understanding of this remarkable protein transport system.

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“…Ether lipids have an alkyl or alkenyl chain on one or more carbons of the glycerol backbone bonded through an ether or vinyl linkage, rather than the usual ester linkage. The physiological roles of ether lipids are not well understood, but they have been implicated in maintaining physicochemical properties of cell membranes, such as membrane fluidity, membrane fusion events, and lipid raft microdomains (9,10). Certain ether lipids, such as lysophosphatidic acid-ether (LPAe) or platelet-activating factor-ether (PAFe), are signaling molecules that have been shown to possess bioactive and even oncogenic properties through binding specific receptors (11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity

Benjamin

Cozzo

et al. 2013

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

182

186

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Aberrant lipid metabolism is an established hallmark of cancer cells. In particular, ether lipid levels have been shown to be elevated in tumors, but their specific function in cancer remains elusive. We show here that the metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the synthesis of ether lipids, is up-regulated across multiple types of aggressive human cancer cells and primary tumors. We demonstrate that ablation of AGPS in cancer cells results in reduced cell survival, cancer aggressiveness, and tumor growth through altering the balance of ether lipid, fatty acid, eicosanoid, and fatty acidderived glycerophospholipid metabolism, resulting in an overall reduction in the levels of several oncogenic signaling lipids. Taken together, our results reveal that AGPS, in addition to maintaining ether lipids, also controls cellular utilization of fatty acids, favoring the generation of signaling lipids necessary for promoting the aggressive features of cancer.cancer metabolism | metabolomics | lipid signaling lysophosphatidic acid | eicosanoids

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Functions and biosynthesis of plasmalogens in health and disease

Cited by 357 publications

References 132 publications

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity

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