scholarly journals The role of neutral lipid nanospheres in Plasmodium falciparum haem crystallization

2007 ◽  
Vol 402 (1) ◽  
pp. 197-204 ◽  
Author(s):  
John M. Pisciotta ◽  
Isabelle Coppens ◽  
Abhai K. Tripathi ◽  
Peter F. Scholl ◽  
Joel Shuman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Neutral Lipid ◽  
Membrane Lipids ◽  
Neutral Lipids ◽  
Close Association ◽  
Subcellular Fractionation ◽  
Digestive Vacuole ◽  
Lipid Mixture ◽  
Intracellular Mechanism

The intraerythrocytic malaria parasite constructs an intracellular haem crystal, called haemozoin, within an acidic digestive vacuole where haemoglobin is degraded. Haem crystallization is the target of the widely used antimalarial quinoline drugs. The intracellular mechanism of molecular initiation of haem crystallization, whether by proteins, polar membrane lipids or by neutral lipids, has not been fully substantiated. In the present study, we show neutral lipid predominant nanospheres, which envelop haemozoin inside Plasmodium falciparum digestive vacuoles. Subcellular fractionation of parasite-derived haemozoin through a dense 1.7 M sucrose cushion identifies monoacylglycerol and diacylglycerol neutral lipids as well as some polar lipids in close association with the purified haemozoin. Global MS lipidomics detects monopalmitic glycerol and monostearic glycerol, but not mono-oleic glycerol, closely associated with haemozoin. The complex neutral lipid mixture rapidly initiates haem crystallization, with reversible pH-dependent quinoline inhibition associated with quinoline entry into the neutral lipid microenvironment. Neutral lipid nanospheres both enable haem crystallization in the presence of high globin concentrations and protect haem from H2O2 degradation. Conceptually, the present study shifts the intracellular microenvironment of haem crystallization and quinoline inhibition from a polar aqueous location to a non-polar neutral lipid nanosphere able to exclude water for efficient haem crystallization.

scholarly journals An essential vesicular-trafficking phospholipase mediates neutral lipid synthesis and contributes to hemozoin formation in Plasmodium falciparum

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mohd Asad ◽  
Yoshiki Yamaryo-Botté ◽  
Mohammad E. Hossain ◽  
Vandana Thakur ◽  
Shaifali Jain ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Neutral Lipid ◽  
Neutral Lipids ◽  
Lipid Synthesis ◽  
Large Family ◽  
Degradation Pathway ◽  
Food Vacuole ◽  
Parasite Growth ◽  
Lipid Homeostasis ◽  
Parasite Development

Abstract Background Plasmodium falciparum is the pathogen responsible for the most devastating form of human malaria. As it replicates asexually in the erythrocytes of its human host, the parasite feeds on haemoglobin uptaken from these cells. Heme, a toxic by-product of haemoglobin utilization by the parasite, is neutralized into inert hemozoin in the food vacuole of the parasite. Lipid homeostasis and phospholipid metabolism are crucial for this process, as well as for the parasite’s survival and propagation within the host. P. falciparum harbours a uniquely large family of phospholipases, which are suggested to play key roles in lipid metabolism and utilization. Results Here, we show that one of the parasite phospholipase (P. falciparum lysophospholipase, PfLPL1) plays an essential role in lipid homeostasis linked with the haemoglobin degradation and heme conversion pathway. Fluorescence tagging showed that the PfLPL1 in infected blood cells localizes to dynamic vesicular structures that traffic from the host-parasite interface at the parasite periphery, through the cytosol, to get incorporated into a large vesicular lipid rich body next to the food-vacuole. PfLPL1 is shown to harbour enzymatic activity to catabolize phospholipids, and its transient downregulation in the parasite caused a significant reduction of neutral lipids in the food vacuole-associated lipid bodies. This hindered the conversion of heme, originating from host haemoglobin, into the hemozoin, and disrupted the parasite development cycle and parasite growth. Detailed lipidomic analyses of inducible knock-down parasites deciphered the functional role of PfLPL1 in generation of neutral lipid through recycling of phospholipids. Further, exogenous fatty-acids were able to complement downregulation of PfLPL1 to rescue the parasite growth as well as restore hemozoin levels. Conclusions We found that the transient downregulation of PfLPL1 in the parasite disrupted lipid homeostasis and caused a reduction in neutral lipids essentially required for heme to hemozoin conversion. Our study suggests a crucial link between phospholipid catabolism and generation of neutral lipids (TAGs) with the host haemoglobin degradation pathway.

scholarly journals Neutral-Lipid Analysis Reveals Elevation of Acylglycerols and Lack of Cholesterol Esters in Plasmodium falciparum-Infected Erythrocytes

2003 ◽  
Vol 2 (5) ◽  
pp. 1128-1131 ◽  
Author(s):  
Parwez Nawabi ◽  
Athanasios Lykidis ◽  
Darder Ji ◽  
Kasturi Haldar
Keyword(s):  
Plasmodium Falciparum ◽  
Toxoplasma Gondii ◽  
Neutral Lipid ◽  
Lipid Analysis ◽  
Neutral Lipids ◽  
Blood Stage ◽  
High Mass ◽  
Cholesterol Esters ◽  
Lipid Species

ABSTRACT Here we show that blood-stage Plasmodium falciparum organisms accumulate a high mass of triacylglycerol and diacylglycerol. However, we failed to detect cholesterol esters, a second neutral lipid species reported to be important for a related apicomplexan, Toxoplasma gondii. Evidence for P. falciparum and T. gondii homologues of acyl coenzyme A:diacylglycerol acyltransferase suggests that acylglycerols may be the conserved neutral lipids in apicomplexans.

scholarly journals Role of chirality in peptide-induced formation of cholesterol-rich domains

2005 ◽  
Vol 390 (2) ◽  
pp. 541-548 ◽  
Author(s):  
Richard M. Epand ◽  
Scott D. Rychnovsky ◽  
Jitendra D. Belani ◽  
Raquel F. Epand
Keyword(s):  
Membrane Lipids ◽  
Specific Binding ◽  
Binding Pocket ◽  
Small Peptides ◽  
Axonal Membrane ◽  
Lipid Mixture ◽  
Transition Enthalpy ◽  
Lipid Organization ◽  
Chiral Specificity

The chiral specificity of the interactions of peptides that induce the formation of cholesterol-rich domains has not been extensively investigated. Both the peptide and most lipids are chiral, so there is a possibility that interactions between peptide and lipid could require chiral recognition. On the other hand, in our models with small peptides, the extent of folding of the peptide to form a specific binding pocket is limited. We have determined that replacing cholesterol with its enantiomer, ent-cholesterol, alters the modulation of lipid organization by peptides. The phase-transition properties of SOPC (1-stearoyl-2-oleoylphosphatidylcholine):cholesterol [in a 6:4 ratio with 0.2 mol% PtdIns(4,5)P2] are not significantly altered when ent-cholesterol replaces cholesterol. However, in the presence of 10 mol% of a 19-amino-acid, N-terminally myristoylated fragment (myristoyl-GGKLSKKKKGYNVNDEKAK-amide) of the protein NAP-22 (neuronal axonal membrane protein), the lipid mixture containing cholesterol undergoes separation into cholesterol-rich and cholesterol-depleted domains. This does not occur when ent-cholesterol replaces cholesterol. In another example, when N-acetyl-Leu-Trp-Tyr-Ile-Lys-amide (N-acetyl-LWYIK-amide) is added to SOPC:cholesterol (7:3 ratio), there is a marked increase in the transition enthalpy of the phospholipid, indicating separation of a cholesterol-depleted domain of SOPC. This phenomenon completely disappears when ent-cholesterol replaces cholesterol. The all-D-isomer of N-acetyl-LWYIK-amide also induces the formation of cholesterol-rich domains with natural cholesterol, but does so to a lesser extent with ent-cholesterol. Thus specific peptide chirality is not required for interaction with cholesterol-containing membranes. However, a specific chirality of membrane lipids is required for peptide-induced formation of cholesterol-rich domains.

scholarly journals A lysophospholipase plays role in generation of neutral-lipids required for hemozoin formation in malaria parasite

2019 ◽  
Author(s):  
Mohd Asad ◽  
Yoshiki Yamaryo-Botté ◽  
Mohammad E. Hossain ◽  
Vandana Thakur ◽  
Shaifali Jain ◽  
...  
Keyword(s):  
Neutral Lipid ◽  
Malaria Parasite ◽  
Neutral Lipids ◽  
Phospholipid Metabolism ◽  
Food Vacuole ◽  
Specific Role ◽  
Lipid Homeostasis ◽  
Knock Down ◽  
Parasite Survival

AbstractPhospholipid metabolism is crucial for membrane dynamics in malaria parasites during entire cycle in the host cell. Plasmodium falciparum harbours several members of phospholipase family, which play key role in phospholipid metabolism. Here we have functionally characterized a parasite lysophospholipase (PfLPL1) with a view to understand its role in lipid homeostasis. We used a regulated fluorescence affinity tagging, which allowed endogenous localization and transient knock-down of the protein. PffLPL1localizes to dynamic vesicular structures that traffic from parasite periphery, through the cytosol to get associated as a multi-vesicular neutral lipid rich body next to the food-vacuole during blood stages. Down-regulation of the PfLPL1 disrupted parasite lipid-homeostasis leading to significant reduction of neutral lipids in lipid-bodies. This hindered conversion of heme to hemozoin, leading to food-vacuole abnormalities, which in turn disrupted parasite development cycle and significantly inhibited parasite growth. Detailed lipidomic analyses of inducible knock-down parasites confirmed role of PfLPL1 in generation of neutral lipid through recycling of phospholipids. Our study thus suggests a specific role of PfLPL1 to generate neutral lipids in the parasite, which are essential for parasite survival.ImportancePresent study was undertaken with a view to understand the functional role of a unique lipase (lysophopholipase, PfLPL1) of the human malaria parasite. We utilized genetic approaches for GFP tagging as well as to knock-down the target protein in the parasite. Our studies showed that PfLPL1 associates closely with the lysosome like organelle in the parasite, the food-vacuole. During the blood stage parasite cycle, the food-vacuole is involved in degradation of host haemoglobin and conversion of heme to hemozoin. Genetic knock-down approaches and detailed lipidomic studies confirmed that PfLPL1 protein plays key role in generation of neutral lipid stores in the parasite; neutral lipids are essentially required for hemozoin formation in the parasite, a vital function of the food-vacuole. Overall, this study identified specific role of PfLPL1 in the parasite which is essential for parasite survival.

On the Role of Transferrin in 67Ga Uptake by Tumor Cells

1988 ◽  
Vol 27 (04) ◽  
pp. 151-153
Author(s):  
P. Thouvenot ◽  
F. Brunotte ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Specific Binding ◽  
Subcellular Fractionation ◽  
Animal Blood ◽  
Tumor Bearing ◽  
Cell Structures ◽  
The Difference ◽  
Sarcoma Cells ◽  
In Vitro Uptake

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about ii/io of 67Ga and 1/5o of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences

The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View

2018 ◽  
Vol 15 (13) ◽  
pp. 1191-1212 ◽  
Author(s):  
Botond Penke ◽  
Gábor Paragi ◽  
János Gera ◽  
Róbert Berkecz ◽  
Zsolt Kovács ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathways ◽  
Membrane Lipids ◽  
Specific Protein ◽  
Dietary Factors ◽  
Lipid Signaling ◽  
Special Role ◽  
Aβ Peptides

Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer’s disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions. The current review focuses on pathological alterations of membrane lipids (cholesterol, glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides insight in the current understanding of biological membranes, their lipid structures and functions, as well as their role as potential therapeutic targets. Novel methods for studying the membrane structure and lipid composition will be reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis of AD will be shortly summarized. Interactions of Aβ peptides with the cell membrane and different subcellular organelles are reviewed. Next, the details of the most important lipid signaling pathways, including the role of the plasma membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2-nonenal may play a special role in the initiation of the pathogenesis of AD and thus the “calpain-cathepsin hypothesis” of AD is highlighted. Finally, the most important lipid dietary factors and their possible use and efficacy in the prevention of AD are discussed.

scholarly journals Mammary gland adipocytes in lactation cycle, obesity and breast cancer

2021 ◽  
Author(s):  
Georgia Colleluori ◽  
Jessica Perugini ◽  
Giorgio Barbatelli ◽  
Saverio Cinti
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Close Association ◽  
Critical Role ◽  
Exocrine Gland ◽  
Plastic Properties ◽  
Lactation Cycle ◽  
Gland Development

AbstractThe mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG’s proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG’s adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.

scholarly journals The Role of Fungi in the Cocoa Production Chain and the Challenge of Climate Change

2021 ◽  
Vol 7 (3) ◽  
pp. 202
Author(s):  
Johannes Delgado-Ospina ◽  
Junior Bernardo Molina-Hernández ◽  
Clemencia Chaves-López ◽  
Gianfranco Romanazzi ◽  
Antonello Paparella
Keyword(s):  
Climate Change ◽  
Fungal Infections ◽  
Close Association ◽  
Pathogenic Fungi ◽  
Fungal Species ◽  
Mitigation Strategies ◽  
Plant Diseases ◽  
Production Chain ◽  
Cocoa Production

Background: The role of fungi in cocoa crops is mainly associated with plant diseases and contamination of harvest with unwanted metabolites such as mycotoxins that can reach the final consumer. However, in recent years there has been interest in discovering other existing interactions in the environment that may be beneficial, such as antagonism, commensalism, and the production of specific enzymes, among others. Scope and approach: This review summarizes the different fungi species involved in cocoa production and the cocoa supply chain. In particular, it examines the presence of fungal species during cultivation, harvest, fermentation, drying, and storage, emphasizing the factors that possibly influence their prevalence in the different stages of production and the health risks associated with the production of mycotoxins in the light of recent literature. Key findings and conclusion: Fungi associated with the cocoa production chain have many different roles. They have evolved in a varied range of ecosystems in close association with plants and various habitats, affecting nearly all the cocoa chain steps. Reports of the isolation of 60 genera of fungi were found, of which only 19 were involved in several stages. Although endophytic fungi can help control some diseases caused by pathogenic fungi, climate change, with increased rain and temperatures, together with intensified exchanges, can favour most of these fungal infections, and the presence of highly aggressive new fungal genotypes increasing the concern of mycotoxin production. For this reason, mitigation strategies need to be determined to prevent the spread of disease-causing fungi and preserve beneficial ones.

scholarly journals Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion

2010 ◽  
Vol 51 (7) ◽  
pp. 1747-1760 ◽  
Author(s):  
Misbaudeen Abdul-Hammed ◽  
Bernadette Breiden ◽  
Matthew A. Adebayo ◽  
Jonathan O. Babalola ◽  
Günter Schwarzmann ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Membrane Lipids ◽  
Endosomal Membrane
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