- Email: [email protected]
Lipidomics and functional lipid biology
Biochimie 130 (2016) 1e3
Contents lists available at ScienceDirect
Biochimie journal homepage: www.elsevier.com/locate/biochi
Editorial
Lipidomics and functional lipid biology
Lipids are small hydrophobic molecules that carry out a multitude of crucial biological roles. For example, the capacity of the non-polar acyl chains of lipids to self-associate in water is the physical basis for spontaneous membrane formation that enables cells to segregate their internal constituents from the external environment. This fundamental process is repeated within nucleated cells to form discrete organelles allowing the formation of intracellular specific compartments. Whereas a single lipid species can form a physical barrier to unregulated solute diffusion, membrane lipids in eukaryotic cells present a remarkable structural diversity. Furthermore, the lipid composition and distribution across membrane bilayers show striking variations allowing changes in physical membrane properties such as bilayer thickness, lipid packing density and surface charge that mark the transition between different membrane compartments. In addition to these structural roles, lipids also store energy and they function as signaling molecules in cellular response pathways. Modification of lipid levels in the human body, as occurs in obesity, diabetes, autoimmunity or lipid metabolism alteration, leads to dysfunction and disease in many organs. The international GERLI meeting “Lipids in Agronomy, Health and Disease” which was held in Bischoffsheim near Strasbourg (France) at the crossroads with Germany and Switzerland in October 2015 provided the impetus for publishing this special issue entitled “Lipidomics and Functional Lipid Biology”. The meeting was the 11th of a series of annual conferences devoted to the review of current research efforts in lipidomics. The association GERLI (Groupe d'Etude et de Recherche en LIpidomique) is active in lipid sciences since 1978 and moved a decade ago to the era of lipidomics, studying molecular and cellular biology of lipids in all states. The meeting was organized in several different sessions devoted to the chemical and physical lipid analysis, lipidomics as a discovery tool, lipid transport, lipid modification of proteins and finally to the role of lipid in various diseases including cancer and neurodegeneration. Plenary lectures were given by Gherard Liebisch and Yvon Le Maho on quantitative profiling of lipids and lipid depletion and refeeding €l Lemie re and Joain fasting animals, respectively. In addition Joe chim Moser von Filseck, the 2015 GERLI-PhD award winners, presented their work on the role of actin cytoskeleton in controlling membrane shape, and sterol transport and homeostasis, respectively. The special issue comprises 15 mini-reviews and 6 original articles, which exemplify all these aspects. The co-delivery of drugs with distinct mechanism of action and targeting diverse cell types and/or different signaling pathways has recently emerged in the treatment of various disease as it offers the possibility to reduce effective doses and thus limit undesired side
http://dx.doi.org/10.1016/j.biochi.2016.10.004 0300-9084/© 2016 Published by Elsevier B.V.
effects. In this context the delivery of drugs using nanoscale systems represents another level of control for effective limited distribution and bioavailability. Couvreur and colleagues describe the design of a novel multidrug nanocarrier, based on the covalent coupling of squalene to drug molecules and subsequent selfassembling as nanoparticles. In the same line, traditional vaccines made of inactivated organism or toxins are known to occasionally trigger side effects. Liposome vesicles made of phospholipids have been shown to be able to deliver a large range of molecules including immune-reactive ones. Pons and colleagues showed that various types of liposomal vaccine administered in the nasal cavity or in the whole respiratory tract have effective immunization capacity with effectiveness at low doses of vaccine and adjuvant. Among glycolipid surfactants, bolaamphiphiles are sugar based compounds with two hydrophilic heads connected by a hydrophobic carbon chain that have also shown some potential for the development of efficient and low cost lipid-based drug delivery systems. Using different biomimetic membranes Nasir and colleagues studied the interaction with two sugar-based bolaamphiphiles, specifically evaluating the impact of sterol presence in membranes. The unlimited and elegant potential of biomimetics to simplify complex re and structures and living systems is nicely illustrated by Lemie colleagues who monitored the cytoskeleton dynamics and mechanics and depicted their effect on cellular membrane reshaping during key biological processes such as cell division and motility. Oenology is an important cultural aspect in numerous European areas and this is now also occurring in other parts of the world, but dietary polyphenols present in vegetables and beverages like red wine have also been reported to possess antioxidant properties with potential beneficial health implications. The work of Furlan and colleagues uses non-invasive solid-state NMR spectroscopy to study the influence of grape polyphenols and ethanol on the degree of organization of the lipid membrane in the presence of various cholesterol levels. It was clearly shown that lipids, although rarely considered in oenology until now, may become key players in the issue of wine tasting. Oily seeds like almonds and other plant materials contain phytoprostanes, that were extensively studied by Durand and co-workers. Phytoprostanes are non-enzymatic peroxidation products of a-linolenic acid that are thought to contribute to the healthy mediterranean diet. These oxidized lipids share a comparable production pathway as other cyclic oxygenated metabolites, namely, isoprostanes and isofuranes, that derive from arachidonic acid in mammals. Collectively, the diverse classes of phytofurans, isofurans, and also neurofurans stand as valuable biomarkers for oxydative stress. In addition, their potential activity in plant defense mechanisms, their role in brain metabolism and
2
Editorial / Biochimie 130 (2016) 1e3
neurological disorders and their potent anti-inflammatory activity have stimulated a comprehensive profiling in various biological systems using mass spectrometry supported by a considerable effort in synthetic chemistry for the production of authentic standards. This will enable further research to qualify better oxidative stress and the health status of patients. High performance mass spectrometryebased lipidomics methods expand the inventory of lipid species and allow their unprecedented quantification. Constant progress in mass spectrometry, mass analysers and instruments pave the way for a better understanding of fragmentation pathways, ion formation and therefore structural elucidation of analytes. This is demonstrated in a contribution by Hsu, on the classification of ceramides in ten major families after these were fragmented by electrospray in a linear ion trap (acronym, LIT) allowing multi-stage mass spectrometric methods of analysis. Such methods differentiate ceramide molecular species and isomers in great detail, a prerequisite to functional studies. In eukaryotes, sphingolipids are essential constituents of plasma membrane and crucial signaling molecules. In recent years, the fast understanding of their biosynthesis in a diverse array of model organisms was tightly related to the emergence of these new lipidomics techniques. At present, sphingolipid biology benefits from the implementation of probes, stable isotope tracers, and alkyne-azide conjugated probes known as click chemistry-based probes to study fluxes, regulation, distribution and function of specific lipids, a series of tools reviewed by Martí~e s and Schneiter. The development of molecular tools nez-Montan for imaging approaches is reviewed in this special issue by Hullin-Matsuda and colleagues, pertaining to the lipid-binding characteristics of toxins (the bacterial cinnamycin and duramycin, and the fungal aegerolysins) to probe phosphatidylethanolamine and ceramide phosphoethanolamine cellular distribution, for instance in Trypasonoma developmental stages. In the case of plants, progress in lipidomics results in refined lipid profiles comprising several hundreds of metabolites of which some were considered as over-looked or neglected until recent years but proven to be essential in biological processes such as flowering, seed development or oil synthesis and deposition, just to quote a few. The integration of lipidomics and genomics provides a comprehensive picture of those processes where changes in lipid profiles and in the orchestration of genome expression lead to gene discovery. As such, lipidomics is pointed out by Brotman and colleagues as a prominent and straightforward tool to unravel biological roles of the wealth of lipid molecules. Furthermore, genome wide association studies in crop plants demonstrated the link between lipidomes and agronomic traits of paramount importance for breeding strategies. Contrasting with mass spectrometry, NMR based imaging techniques as non-invasive analytical methods are shown to open up many possibilities to visualize and quantify lipids without loss of the cellular context and integrity, for instance in plant seeds. An accurate overview of the current status and future prospects of the dynamic study of lipid deposition in plant embryo, seeds and fruits is delivered by Borisjuk and colleagues, as a strong advocacy to foster this new field in plant biology. The molecular identification of the anti-estrogen binding sites has suggested mechanisms that could explain the acquired resistance to tamoxifen in breast cancer, but also has allowed production of the tumor suppressor metabolite dendrogenin A. Silvente-Poirot and colleagues review the different steps of this journey, highlighting a new mammalian metabolic pathway at the crossroads of histamine and cholesterol metabolism. Organelles trafficking constitute in mammalian cells an essential process for lipid transport but recent evidence has suggested that certain lipids are transported by lipid transfer proteins at sites of close apposition of two organelles called membrane contact sites. Moser von Filseck and Drin review
the recent data that have shown that ORP/Osh family transport sterols and phosphatidylserine to the Golgi and plasma membrane, respectively, through counter-exchange for the phosphoinositide phosphatidylinositol 4-phosphate. Strikingly, phosphoinositide/sterol exchanges appear hijacked by various virus strains to generate replication organelles, suggesting that actors of these novel lipid transport pathway could be relevant pharmaceutical targets. Most antimicrobial peptides are thought to predominantly act through membrane lytic activity. Rautenbach and colleagues present evidence that the cyclic decapeptides tyrocidines interfere with fungal development with some selectivity for ergosterol (not present in mammalian membranes) and possibly affecting lipid microdomains, but also suggesting that components of cell wall such as b-glucan could be additional targets of the aromatic dipeptide containing tyrocidines. In a second manuscript they also review the recent advances in our knowledge of how natural antifungal peptides target fungi and discuss the option to be or not be membrane active for effective antifungal activity. Cellular membranes are now considered as dynamic interfaces providing a molecular environment favorable to the activity of membrane-associated proteins. Interestingly, variations in membrane lipid composition, whether quantitative or qualitative, crucially regulate membrane protein functionalities. Indeed, a variety of alterations in brain lipid composition have been associated with the processes of normal and pathological aging, especially related to neurodegeneration. Establishing a direct cause-andeffect relationship between these complex modifications in cerebral membranes and the process of cognitive decline is the focus of several reviews. Sandhoff summarizes recent findings on the regulation of sphingolipid catabolism and cholesterol secretion from the endosomal compartment by lipid modifiers, suggesting that lipid affect the genotype-phenotype relationship observed in patients with lysosomal diseases. Kuech and colleagues emphasize their review on membrane trafficking defects observed in various lysosomal diseases such as Niemann-Pick type C, where export of LDL-derived cholesterol is altered. They also discuss the current strategies that could improve folding of defective lysosomal hydrolase, the main therapeutical target to date for these diseases. Among polyunsaturated fatty acids docosahexaenoic acid (DHA) is an omega-3 lipid enriched in the brain and the level of which is decreased in various neurological disorders, including Alzheimer and Parkinson diseases. Since the precursor of DHA is not synthesized and poorly converted into DHA in mammals, several studies conducted both in animal models and in humans suggest that an adequate dietary intake of omega-3 lipids can prevent cognitive decline and attenuate the physiological disturbances of the brain that are associated with ageing or with neurologic disorders. Lo Van and colleagues review evidence suggesting that DHA is preferentially incorporated when esterified within lysophospholipids and describe the potential positive effects of DHA and its metabolites on brain diseases. Another review by Colin and colleagues focuses on the potential role of DHA in the spatial membrane organization and on the formation and maintenance of membrane microdomains, known as rafts, suggesting that targeting microdomain preservation through DHA supplementation could maintain effective cerebral function. Arachidonic acid is the second major polyunsaturated fatty acid in mammalian cells and is mainly produced by the activity of phospholipases A2. Over the last half century the levels of this omega-6 lipid in western diets has greatly increased, mostly at the expense of omega-3 lipids. Thomas and colleagues review the latest evidences suggesting that arachidonic acid also influences the occurrence and the development of Alzheimer's disease and describe the mechanisms potentially involved, with the notion that the omega3/omega6 ratio is important. Finally the work of Tabet and coworkers reviews the latest evidence showing a
Editorial / Biochimie 130 (2016) 1e3
deregulation of the diacylglycerol (DAG)/phosphatidic acid (PA) homeostasis in neurons of the fragile X mouse model, the most common cause of inherited intellectual disability. In fact diacylglycerol kinase k appears to be the main target of the fragile X mental retardation protein and could therefore represent a novel therapeutic target for the treatment of Fragile X syndrome. Altogether these reviews highlight the importance of specific lipid balance (omega3/ omega6; DAG/PA) and for the first time raise the possibility of treatment for various diseases. To conclude, this special issue thus provides a series of reviews and original articles covering various aspects of lipids biophysics and properties within membranes to their function in cell physiology and pathologies, opening new research avenues.
acknowledge the support of the Regional Editor, Dr. Claude Forest, and the skill of the Editorial Assistant Malika Hassini, for assembling this special issue. Hubert Schaller* Institut de Biologie Moleculaire des Plantes (IBMP), UPR-2357 Centre National de la Recherche Scientifique & Universit e de Strasbourg, 12 rue du G en eral Zimmer, 67084 Strasbourg, France Nicolas Vitale* Institut des Neurosciences Cellulaires et Int egratives (INCI), UPR-3212 Centre National de la Recherche Scientifique & Universit e de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France *
Acknowledgements We are particularly grateful to all the researchers enthusiastically answered our invitation to contribute this special issue of Biochimie, and to the dedicated who helped us to reach the highest standard. We
3
who have articles to reviewers gratefully
Corresponding authors. E-mail addresses: [email protected] (H. Schaller), [email protected] (N Vitale)
Contents lists available at ScienceDirect
Biochimie journal homepage: www.elsevier.com/locate/biochi
Editorial
Lipidomics and functional lipid biology
Lipids are small hydrophobic molecules that carry out a multitude of crucial biological roles. For example, the capacity of the non-polar acyl chains of lipids to self-associate in water is the physical basis for spontaneous membrane formation that enables cells to segregate their internal constituents from the external environment. This fundamental process is repeated within nucleated cells to form discrete organelles allowing the formation of intracellular specific compartments. Whereas a single lipid species can form a physical barrier to unregulated solute diffusion, membrane lipids in eukaryotic cells present a remarkable structural diversity. Furthermore, the lipid composition and distribution across membrane bilayers show striking variations allowing changes in physical membrane properties such as bilayer thickness, lipid packing density and surface charge that mark the transition between different membrane compartments. In addition to these structural roles, lipids also store energy and they function as signaling molecules in cellular response pathways. Modification of lipid levels in the human body, as occurs in obesity, diabetes, autoimmunity or lipid metabolism alteration, leads to dysfunction and disease in many organs. The international GERLI meeting “Lipids in Agronomy, Health and Disease” which was held in Bischoffsheim near Strasbourg (France) at the crossroads with Germany and Switzerland in October 2015 provided the impetus for publishing this special issue entitled “Lipidomics and Functional Lipid Biology”. The meeting was the 11th of a series of annual conferences devoted to the review of current research efforts in lipidomics. The association GERLI (Groupe d'Etude et de Recherche en LIpidomique) is active in lipid sciences since 1978 and moved a decade ago to the era of lipidomics, studying molecular and cellular biology of lipids in all states. The meeting was organized in several different sessions devoted to the chemical and physical lipid analysis, lipidomics as a discovery tool, lipid transport, lipid modification of proteins and finally to the role of lipid in various diseases including cancer and neurodegeneration. Plenary lectures were given by Gherard Liebisch and Yvon Le Maho on quantitative profiling of lipids and lipid depletion and refeeding €l Lemie re and Joain fasting animals, respectively. In addition Joe chim Moser von Filseck, the 2015 GERLI-PhD award winners, presented their work on the role of actin cytoskeleton in controlling membrane shape, and sterol transport and homeostasis, respectively. The special issue comprises 15 mini-reviews and 6 original articles, which exemplify all these aspects. The co-delivery of drugs with distinct mechanism of action and targeting diverse cell types and/or different signaling pathways has recently emerged in the treatment of various disease as it offers the possibility to reduce effective doses and thus limit undesired side
http://dx.doi.org/10.1016/j.biochi.2016.10.004 0300-9084/© 2016 Published by Elsevier B.V.
effects. In this context the delivery of drugs using nanoscale systems represents another level of control for effective limited distribution and bioavailability. Couvreur and colleagues describe the design of a novel multidrug nanocarrier, based on the covalent coupling of squalene to drug molecules and subsequent selfassembling as nanoparticles. In the same line, traditional vaccines made of inactivated organism or toxins are known to occasionally trigger side effects. Liposome vesicles made of phospholipids have been shown to be able to deliver a large range of molecules including immune-reactive ones. Pons and colleagues showed that various types of liposomal vaccine administered in the nasal cavity or in the whole respiratory tract have effective immunization capacity with effectiveness at low doses of vaccine and adjuvant. Among glycolipid surfactants, bolaamphiphiles are sugar based compounds with two hydrophilic heads connected by a hydrophobic carbon chain that have also shown some potential for the development of efficient and low cost lipid-based drug delivery systems. Using different biomimetic membranes Nasir and colleagues studied the interaction with two sugar-based bolaamphiphiles, specifically evaluating the impact of sterol presence in membranes. The unlimited and elegant potential of biomimetics to simplify complex re and structures and living systems is nicely illustrated by Lemie colleagues who monitored the cytoskeleton dynamics and mechanics and depicted their effect on cellular membrane reshaping during key biological processes such as cell division and motility. Oenology is an important cultural aspect in numerous European areas and this is now also occurring in other parts of the world, but dietary polyphenols present in vegetables and beverages like red wine have also been reported to possess antioxidant properties with potential beneficial health implications. The work of Furlan and colleagues uses non-invasive solid-state NMR spectroscopy to study the influence of grape polyphenols and ethanol on the degree of organization of the lipid membrane in the presence of various cholesterol levels. It was clearly shown that lipids, although rarely considered in oenology until now, may become key players in the issue of wine tasting. Oily seeds like almonds and other plant materials contain phytoprostanes, that were extensively studied by Durand and co-workers. Phytoprostanes are non-enzymatic peroxidation products of a-linolenic acid that are thought to contribute to the healthy mediterranean diet. These oxidized lipids share a comparable production pathway as other cyclic oxygenated metabolites, namely, isoprostanes and isofuranes, that derive from arachidonic acid in mammals. Collectively, the diverse classes of phytofurans, isofurans, and also neurofurans stand as valuable biomarkers for oxydative stress. In addition, their potential activity in plant defense mechanisms, their role in brain metabolism and
2
Editorial / Biochimie 130 (2016) 1e3
neurological disorders and their potent anti-inflammatory activity have stimulated a comprehensive profiling in various biological systems using mass spectrometry supported by a considerable effort in synthetic chemistry for the production of authentic standards. This will enable further research to qualify better oxidative stress and the health status of patients. High performance mass spectrometryebased lipidomics methods expand the inventory of lipid species and allow their unprecedented quantification. Constant progress in mass spectrometry, mass analysers and instruments pave the way for a better understanding of fragmentation pathways, ion formation and therefore structural elucidation of analytes. This is demonstrated in a contribution by Hsu, on the classification of ceramides in ten major families after these were fragmented by electrospray in a linear ion trap (acronym, LIT) allowing multi-stage mass spectrometric methods of analysis. Such methods differentiate ceramide molecular species and isomers in great detail, a prerequisite to functional studies. In eukaryotes, sphingolipids are essential constituents of plasma membrane and crucial signaling molecules. In recent years, the fast understanding of their biosynthesis in a diverse array of model organisms was tightly related to the emergence of these new lipidomics techniques. At present, sphingolipid biology benefits from the implementation of probes, stable isotope tracers, and alkyne-azide conjugated probes known as click chemistry-based probes to study fluxes, regulation, distribution and function of specific lipids, a series of tools reviewed by Martí~e s and Schneiter. The development of molecular tools nez-Montan for imaging approaches is reviewed in this special issue by Hullin-Matsuda and colleagues, pertaining to the lipid-binding characteristics of toxins (the bacterial cinnamycin and duramycin, and the fungal aegerolysins) to probe phosphatidylethanolamine and ceramide phosphoethanolamine cellular distribution, for instance in Trypasonoma developmental stages. In the case of plants, progress in lipidomics results in refined lipid profiles comprising several hundreds of metabolites of which some were considered as over-looked or neglected until recent years but proven to be essential in biological processes such as flowering, seed development or oil synthesis and deposition, just to quote a few. The integration of lipidomics and genomics provides a comprehensive picture of those processes where changes in lipid profiles and in the orchestration of genome expression lead to gene discovery. As such, lipidomics is pointed out by Brotman and colleagues as a prominent and straightforward tool to unravel biological roles of the wealth of lipid molecules. Furthermore, genome wide association studies in crop plants demonstrated the link between lipidomes and agronomic traits of paramount importance for breeding strategies. Contrasting with mass spectrometry, NMR based imaging techniques as non-invasive analytical methods are shown to open up many possibilities to visualize and quantify lipids without loss of the cellular context and integrity, for instance in plant seeds. An accurate overview of the current status and future prospects of the dynamic study of lipid deposition in plant embryo, seeds and fruits is delivered by Borisjuk and colleagues, as a strong advocacy to foster this new field in plant biology. The molecular identification of the anti-estrogen binding sites has suggested mechanisms that could explain the acquired resistance to tamoxifen in breast cancer, but also has allowed production of the tumor suppressor metabolite dendrogenin A. Silvente-Poirot and colleagues review the different steps of this journey, highlighting a new mammalian metabolic pathway at the crossroads of histamine and cholesterol metabolism. Organelles trafficking constitute in mammalian cells an essential process for lipid transport but recent evidence has suggested that certain lipids are transported by lipid transfer proteins at sites of close apposition of two organelles called membrane contact sites. Moser von Filseck and Drin review
the recent data that have shown that ORP/Osh family transport sterols and phosphatidylserine to the Golgi and plasma membrane, respectively, through counter-exchange for the phosphoinositide phosphatidylinositol 4-phosphate. Strikingly, phosphoinositide/sterol exchanges appear hijacked by various virus strains to generate replication organelles, suggesting that actors of these novel lipid transport pathway could be relevant pharmaceutical targets. Most antimicrobial peptides are thought to predominantly act through membrane lytic activity. Rautenbach and colleagues present evidence that the cyclic decapeptides tyrocidines interfere with fungal development with some selectivity for ergosterol (not present in mammalian membranes) and possibly affecting lipid microdomains, but also suggesting that components of cell wall such as b-glucan could be additional targets of the aromatic dipeptide containing tyrocidines. In a second manuscript they also review the recent advances in our knowledge of how natural antifungal peptides target fungi and discuss the option to be or not be membrane active for effective antifungal activity. Cellular membranes are now considered as dynamic interfaces providing a molecular environment favorable to the activity of membrane-associated proteins. Interestingly, variations in membrane lipid composition, whether quantitative or qualitative, crucially regulate membrane protein functionalities. Indeed, a variety of alterations in brain lipid composition have been associated with the processes of normal and pathological aging, especially related to neurodegeneration. Establishing a direct cause-andeffect relationship between these complex modifications in cerebral membranes and the process of cognitive decline is the focus of several reviews. Sandhoff summarizes recent findings on the regulation of sphingolipid catabolism and cholesterol secretion from the endosomal compartment by lipid modifiers, suggesting that lipid affect the genotype-phenotype relationship observed in patients with lysosomal diseases. Kuech and colleagues emphasize their review on membrane trafficking defects observed in various lysosomal diseases such as Niemann-Pick type C, where export of LDL-derived cholesterol is altered. They also discuss the current strategies that could improve folding of defective lysosomal hydrolase, the main therapeutical target to date for these diseases. Among polyunsaturated fatty acids docosahexaenoic acid (DHA) is an omega-3 lipid enriched in the brain and the level of which is decreased in various neurological disorders, including Alzheimer and Parkinson diseases. Since the precursor of DHA is not synthesized and poorly converted into DHA in mammals, several studies conducted both in animal models and in humans suggest that an adequate dietary intake of omega-3 lipids can prevent cognitive decline and attenuate the physiological disturbances of the brain that are associated with ageing or with neurologic disorders. Lo Van and colleagues review evidence suggesting that DHA is preferentially incorporated when esterified within lysophospholipids and describe the potential positive effects of DHA and its metabolites on brain diseases. Another review by Colin and colleagues focuses on the potential role of DHA in the spatial membrane organization and on the formation and maintenance of membrane microdomains, known as rafts, suggesting that targeting microdomain preservation through DHA supplementation could maintain effective cerebral function. Arachidonic acid is the second major polyunsaturated fatty acid in mammalian cells and is mainly produced by the activity of phospholipases A2. Over the last half century the levels of this omega-6 lipid in western diets has greatly increased, mostly at the expense of omega-3 lipids. Thomas and colleagues review the latest evidences suggesting that arachidonic acid also influences the occurrence and the development of Alzheimer's disease and describe the mechanisms potentially involved, with the notion that the omega3/omega6 ratio is important. Finally the work of Tabet and coworkers reviews the latest evidence showing a
Editorial / Biochimie 130 (2016) 1e3
deregulation of the diacylglycerol (DAG)/phosphatidic acid (PA) homeostasis in neurons of the fragile X mouse model, the most common cause of inherited intellectual disability. In fact diacylglycerol kinase k appears to be the main target of the fragile X mental retardation protein and could therefore represent a novel therapeutic target for the treatment of Fragile X syndrome. Altogether these reviews highlight the importance of specific lipid balance (omega3/ omega6; DAG/PA) and for the first time raise the possibility of treatment for various diseases. To conclude, this special issue thus provides a series of reviews and original articles covering various aspects of lipids biophysics and properties within membranes to their function in cell physiology and pathologies, opening new research avenues.
acknowledge the support of the Regional Editor, Dr. Claude Forest, and the skill of the Editorial Assistant Malika Hassini, for assembling this special issue. Hubert Schaller* Institut de Biologie Moleculaire des Plantes (IBMP), UPR-2357 Centre National de la Recherche Scientifique & Universit e de Strasbourg, 12 rue du G en eral Zimmer, 67084 Strasbourg, France Nicolas Vitale* Institut des Neurosciences Cellulaires et Int egratives (INCI), UPR-3212 Centre National de la Recherche Scientifique & Universit e de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France *
Acknowledgements We are particularly grateful to all the researchers enthusiastically answered our invitation to contribute this special issue of Biochimie, and to the dedicated who helped us to reach the highest standard. We
3
who have articles to reviewers gratefully
Corresponding authors. E-mail addresses: [email protected] (H. Schaller), [email protected] (N Vitale)