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An Arabidopsis lipid map reveals differences between tissues and dynamic changes throughout development
Abstract
Mass spectrometry is the predominant analytical tool used in the field of plant lipidomics. However, there are many challenges associated with the mass spectrometric detection and identification of lipids due to the highly complex nature of plant lipids. Studies into lipid biosynthetic pathways, gene functions in lipid metabolism, lipid changes during plant growth and development and the holistic examination of the role of plant lipids in environmental stress responses are often hindered. Here, we leveraged a robust pipeline, which we previously established to extract and analyze lipid profiles of different tissues and developmental stages from the plant model Arabidopsis thaliana. We analyzed seven tissues at several different developmental stages and identified more than 200 lipids from each analyzed tissue. The data were used to create a web‐accessible in silico lipid map which has been integrated into an electronic Fluorescent Pictograph (eFP) ‐ browser. This in‐silico library of Arabidopsis lipids allows the visualization and the exploration of the distribution and changes of lipid levels across selected developmental stages. Furthermore, it provides information on the characteristic fragments of lipids and adducts observed in the mass spectrometer and their retention times, which can be used for lipid identification. The Arabidopsis tissue lipid map can be accessed at http://bar.utoronto.ca/efp_arabidopsis_lipid/cgi‐bin/efpWeb.cgi.
... In plant tissues other than seeds, the roles of lipid droplets, composed mainly of triacylglycerols, are increasingly appreciated, largely due to our ability to measure their component triacylglycerol via lipidomics. Quantitative analysis of seed or other tissue extracts containing triacylglycerols by mass spectrometry, with or without chromatography, most often is performed using electrospray ionization in the positive mode [76][77][78][79]. Many methods take advantage of the neutral loss of a fatty acid to form a positively charged diacylglycerol fragment [76][77][78][79]. ...
... Quantitative analysis of seed or other tissue extracts containing triacylglycerols by mass spectrometry, with or without chromatography, most often is performed using electrospray ionization in the positive mode [76][77][78][79]. Many methods take advantage of the neutral loss of a fatty acid to form a positively charged diacylglycerol fragment [76][77][78][79]. Combining information from multiple neutral loss scans or monitoring of multiple transitions (from intact ion to diacylglycerol cation) can be used to define the triacylglycerols in terms of all three fatty acids [76][77][78][79]. ...
... Many methods take advantage of the neutral loss of a fatty acid to form a positively charged diacylglycerol fragment [76][77][78][79]. Combining information from multiple neutral loss scans or monitoring of multiple transitions (from intact ion to diacylglycerol cation) can be used to define the triacylglycerols in terms of all three fatty acids [76][77][78][79]. However, sometimes only the total carbon number: total double bonds or the identity of one fatty acid with the other two combined have been reported (e.g. ...
Twenty years of lipidomics has resulted in improved understanding of the roles of lipids in plants. Lipidomics has led to an increased appreciation of lipid functions in protein regulation, control of cellular pathways, and plant development. Lipidomics has expanded knowledge of the network of alterations in lipids and lipid metabolism during plant stress responses and has played an important role in optimizing the engineering of plants for production of lipid products. Innovations in lipidomic technology and increasing access to genomic and other ‘omic data indicate that the future of lipidomics in plant sciences is very promising.
... The phylogenetic relationship of Δ15 (ω-3) and Δ12 oleate (ω-6) membrane-bound desaturases in chia and other commercially important plants is shown in Figure 5. While the lipid biosynthesis pathways and lipidome in Arabidopsis have been well studied (Li-Beisson et al., 2013;Kehelpannala et al., 2021), the genetic mechanisms that drive the abundant production of PUFAs and their accumulation in chia seeds are only beginning to be understood. Recent studies shed light on FA biosynthesis and the underlying genetic mechanisms that govern the process Gupta et al., 2023;Xue et al., 2023;Zare et al., 2024). ...
... Creating a publicly available web-based database, which includes large-scale transcriptomic comparisons under various conditions and in different tissues, and using the tools available for model plant species can effectively collect such information and accelerate the development of genomic breeding techniques. Developing an optimal lipid extraction technique and a comprehensive lipid database similar to the one created for Arabidopsis (Kehelpannala et al., 2020;Kehelpannala et al., 2021) can help with metabolomic/lipidomic studies on chia. This could provide additional insight into the production and enrichment of ω-3 FAs in chia seeds. ...
Background
Chia (Salvia hispanica L.) seeds have become increasingly popular among health-conscious consumers owing to their high content of ω-3 fatty acids, which provide various health benefits. Comprehensive chemical analyses of the fatty acids and proteins in chia seeds have been conducted, revealing their functional properties. Recent studies have confirmed the high ω-3 content of chia seed oil and have hinted at additional functional characteristics.
Scope
This review article aims to provide an overview of the botanical, morphological and biochemical features of chia plants, seeds and seed mucilage. Additionally, we discuss the recent developments in genetic and molecular research on chia, including the latest transcriptomic and functional studies that examine the genes responsible for chia fatty acid biosynthesis. In recent years, research on chia seeds has shifted its focus from studying the physicochemical characteristics and chemical composition of seeds to understanding the metabolic pathways and molecular mechanisms that contribute to their nutritional benefits. This has led to a growing interest in various pharmaceutical, nutraceutical and agricultural applications of chia. In this context, we discuss the latest research on chia and the questions that remain unanswered, and we identify areas that require further exploration.
Conclusions
Nutraceutical compounds associated with significant health benefits, including ω-3 polyunsaturated fatty acids, proteins and phenolic compounds with antioxidant activity, have been measured in high quantities in chia seeds. However, comprehensive investigations through both in vitro experiments and in vivo animal and controlled human trials are expected to provide greater clarity on the medicinal, antimicrobial and antifungal effects of chia seeds. The recently published genome of chia and gene-editing technologies, such as CRISPR, facilitate functional studies deciphering molecular mechanisms of biosynthesis and metabolic pathways in this crop. This necessitates development of stable transformation protocols and creation of a publicly available lipid database, mutant collection and large-scale transcriptomic datasets for chia.
... Moreover, the results demonstrated that 16:0_18:1_PC was high in chickpea PC, and diverse plasmanyl PC species and docosahexaenoic acid (DHA)-containing PC species were detected in the six types of beans. MS-based lipidomics has also been used to monitor the alteration of lipid species at several different developmental stages of the model plant Arabidopsis thaliana, and more than 200 lipid species from different subclasses have been identified from each developmental stage [74]. In summary, MS-based lipidomics has proven to be a useful technique for determining lipid profiles and has shown excellent performance in monitoring the alteration of lipid species in processed foods or foods affected by environmental factors. ...
With the current advancement in mass spectrometry (MS)-based lipidomics, the knowledge of lipidomes and their diverse roles has greatly increased, enabling a deeper understanding of the action of bioactive lipid molecules in plant- and animal-based foods. This review provides in-depth information on the practical use of MS techniques in lipidomics, including lipid extraction, adduct formation, MS analysis, data processing, statistical analysis, and bioinformatics. Moreover, this contribution demonstrates the effectiveness of MS-based lipidomics for identifying and quantifying diverse lipid species, especially triacylglycerols and phospholipids, in foods. Further, it summarizes the wide applications of MS-based lipidomics in food science, such as for assessing food processing methods, detecting food adulteration, and measuring lipid oxidation in foods. Thus, MS-based lipidomics may be a useful method for identifying the action of individual lipid species in foods.
... Indeed, the vast majority of the panmetabolome of the plant kingdom comes from secondary or specialized metabolites with primary metabolites thought to contribute approximately 1000 metabolites [14], hormones and their derivatives a similar number [15], and volatile organic compounds approximately 500 metabolites (Fernie 2007 [16]). Moreover, over 800 lipid species have been identified to date in plants [17]. When analyzing plant specialized metabolites terpenoides are the most represented class with some 25,000 compounds, followed by alkaloids (12,000) and phenylpropanoids/flavonoids (800) [11]. ...
Whilst the study of metabolites can arguably be traced back several hundred years it began in earnest in the 20th century with studies based on single metabolites or simple metabolic pathways. The advent of metabolomics and in particular the adoption of high-resolution mass spectrometry now means we can faithfully annotate and quantify in excess of 1000 plant metabolites. Whilst this is an impressive leap it falls well short of the estimated number of metabolites in the plant kingdom. This, whilst considerable and important insights have been achieved using commonly utilized approaches, there is a need to improve the coverage of the metabolome. Here, we review three largely complementary strategies (i) methods based on using chemical libraries (ii) methods based on molecular networking and (iii) approaches that link metabolomics and genetic variance. It is our contention that using all three approaches in tandem represents the best approach to tackle this challenge.
The Bio-Analytic Resource for Plant Biology (‘the BAR’, at https://bar.utoronto.ca) is celebrating its 20th year in operation in 2025. The BAR encompasses and provides visualization tools for large ‘omics data sets from plants. The BAR covers data from Arabidopsis, tomato, wheat, barley and 29 other plant species (with data for 2 others to be released soon). These data include nucleotide and protein sequence data, gene expression data, protein-protein and protein–DNA interactions, protein structures, subcellular localizations, and polymorphisms. The data are stored in more than 200 relational databases holding 186 GB of data and are presented to the researchers via web apps. These web apps provide data analysis and visualization tools. Some of the most popular tools are eFP (‘electronic fluorescent pictograph’) Browsers, ePlants and ThaleMine (an Arabidopsis-specific instance of InterMine). The BAR was designated a Global Core Biodata Resource in 2023. Like other GCBRs, the BAR has excellent operational stability, provides access without login requirement, and provides an API for researchers to be able to access BAR data programmatically. We present in this update a new overarching search tool called Gaia that permits easy access to all BAR data, powered by machine learning and artificial intelligence.
Plants and algae play a crucial role in the earth's ecosystems. Through photosynthesis they convert light energy into chemical energy, capture CO2 and produce oxygen and energy-rich organic compounds. Photosynthetic organisms are primary producers and synthesize the essential omega 3 and omega 6 fatty acids. They have also unique and highly diverse complex lipids, such as glycolipids, phospholipids, triglycerides, sphingolipids and phytosterols, with nutritional and health benefits. Plant and algal lipids are useful in food, feed, nutraceutical, cosmeceutical and pharmaceutical industries but also for green chemistry and bioenergy. The analysis of plant and algal lipidomes represents a significant challenge due to the intricate and diverse nature of their composition, as well as their plasticity under changing environmental conditions. Optimization of analytical tools is crucial for an in-depth exploration of the lipidome of plants and algae. This review highlights how lipidomics analytical tools can be used to establish a complete mapping of plant and algal lipidomes. Acquiring this knowledge will pave the way for the use of plants and algae as sources of tailored lipids for both industrial and environmental applications. This aligns with the main challenges for society, upholding the natural resources of our planet and respecting their limits.
The establishment of moss spores is considered a milestone in plant evolution. They harbor protein networks underpinning desiccation tolerance and accumulation of storage compounds that can be found already in algae and that are also utilized in seeds and pollen. Furthermore, germinating spores must produce proteins that drive the transition through heterotrophic growth to the autotrophic plant. To get insight into the plasticity of this proteome, we investigated it at five timepoints of moss (Physcomitrium patens) spore germination and in protonemata and gametophores. The comparison to previously published Arabidopsis proteome data of seedling establishment showed that not only the proteomes of spores and seeds are functionally related, but also the proteomes of germinating spores and young seedlings. We observed similarities with regard to desiccation tolerance, lipid droplet proteome composition, control of dormancy, and β-oxidation and the glyoxylate cycle. However, there were also striking differences. For example, spores lacked any obvious storage proteins. Furthermore, we did not detect homologs to the main triacylglycerol lipase in Arabidopsis seeds, SUGAR DEPENDENT1. Instead, we discovered a triacylglycerol lipase of the oil body lipase family and a lipoxygenase as being the overall most abundant proteins in spores. This finding indicates an alternative pathway for triacylglycerol degradation via oxylipin intermediates in the moss. The comparison of spores to Nicotiana tabacum pollen indicated similarities for example in regards to resistance to desiccation and hypoxia, but the overall developmental pattern did not align as in the case of seedling establishment and spore germination.
Genomics, transcriptomics, and proteomics data mining are some of the interdisciplinary and emerging fields of bioinformatics that are evolving rapidly, making it difficult to predict the magnitude and pace of change. Bioinformatics tools have become an important means for researchers to conduct research. Such tools provide easy access to large datasets spanning genomes, transcriptomes, proteomes, epigenomes, and other ‘omics’ generated over the last decade. This chapter describes the use of bioinformatics tools found in numerous databases, such as Bio-Analytic Resource for Plant Biology, Protein Sequence Analysis and Classification Database (InterPro), Comparative Toxicogenomics Database, Plant Comparative Genomics Portal (Phytozome), Kyoto Encyclopedia of Genes and Genomes, The Arabidopsis Information Resource, and ExplorEnz-Enzyme database (IUBMB). Therefore, this chapter defines data mining as an efficient method of extracting new information or new knowledge from large data sets or databases. However, new information that reflects the underlying biological processes can potentially be useful in biotechnology and biochemical research. Finally, this chapter briefly discusses some of these tools and scenarios that may be useful to scientific researchers.
Arabidopsis sepals coordinate flower opening in the morning as ambient temperature rises; however, the underlying molecular mechanisms are poorly understood. Mutation of one heat shock protein encoding gene, HSP70-16, impaired sepal heat stress responses (HSR), disrupting lipid metabolism, especially sepal cuticular lipids, leading to abnormal flower opening. To further explore, to what extent, lipids play roles in this process, in this study, we compared lipidomic changes in sepals of hsp70-16 and vdac3 (mutant of a voltage-dependent anion channel, VDAC3, an HSP70-16 interactor) grown under both normal (22 °C) and mild heat stress (27 °C, mild HS) temperatures. Under normal temperature, neither hsp70-16 nor vdac3 sepals showed significant changes in total lipids; however, vdac3 but not hsp70-16 sepals exhibited significant reductions in the ratios of all detected 11 lipid classes, except the monogalactosyldiacylglycerols (MGDGs). Under mild HS temperature, hsp70-16 but not vdac3 sepals showed dramatic reduction in total lipids. In addition, vdac3 sepals exhibited a significant accumulation of plastidic lipids, especially sulfoquinovosyldiacylglycerols (SQDGs) and phosphatidylglycerols (PGs), whereas hsp70-16 sepals had a significant accumulation of triacylglycerols (TAGs) and simultaneous dramatic reductions in SQDGs and phospholipids (PLs), such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and phosphatidylserines (PSs). These findings revealed that the impact of mild HS on sepal lipidome is influenced by genetic factors, and further, that HSP70-16 and VDAC3 differently affect sepal lipidomic responses to mild HS. Our studies provide a lipidomic insight into functions of HSP and VDAC proteins in the plant’s HSR, in the context of floral development.
Supplementary Information
The online version contains supplementary material available at 10.1007/s42994-023-00103-x.
Background
The plant lipidome is highly complex, and the composition of lipids in different tissues as well as their specific functions in plant development, growth and stress responses have yet to be fully elucidated. To do this, efficient lipid extraction protocols which deliver target compounds in solution at concentrations adequate for subsequent detection, quantitation and analysis through spectroscopic methods are required. To date, numerous methods are used to extract lipids from plant tissues. However, a comprehensive analysis of the efficiency and reproducibility of these methods to extract multiple lipid classes from diverse tissues of a plant has not been undertaken.
Results
In this study, we report the comparison of four different lipid extraction procedures in order to determine the most effective lipid extraction protocol to extract lipids from different tissues of the model plant Arabidopsis thaliana.
Conclusion
While particular methods were best suited to extract different lipid classes from diverse Arabidopsis tissues, overall a single-step extraction method with a 24 h extraction period, which uses a mixture of chloroform, isopropanol, methanol and water, was the most efficient, reproducible and the least labor-intensive to extract a broad range of lipids for untargeted lipidomic analysis of Arabidopsis tissues. This method extracted a broad range of lipids from leaves, stems, siliques, roots, seeds, seedlings and flowers of Arabidopsis. In addition, appropriate methods for targeted lipid analysis of specific lipids from particular Arabidopsis tissues were also identified.
A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e. annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labelled compounds in metabolic labelling experiments or as internal standards.
This update on lipid classification, nomenclature and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.
Diacylglycerol kinase (DGK) is recognized as the key enzyme of the lipid signaling pathway, which involves the transduction of messages from hormones, neurotransmitters, and immunologic and growth factors. Regarding their essential role in animal physiology, many plant biologists have predicted a similar enzymatic influence in plants. However, a small number of recent studies have revealed the complexity of the involvement of DGK genes in the modulation of plant growth, development, and adaptation in both biotic and abiotic stress conditions. Here, we describe recent discoveries on the role of DGK genes in the plants’ responses to biotic or abiotic stressors. Moreover, we discuss how DGK enzymes regulate plant cellular activities during the adaptation of plants to a readily changing environment. DGK is an enzyme that plays a pivotal role in plant lipid signaling, by catalyzing the phosphorylation of the diacylglycerol (DAG) to phosphatidic acid (PA), which is a crucial molecule in a plant’s metabolic network, leading to its response to various external stresses. DGK enzymes are the principal moderators of PA generation in plant cells; this consequently affects its derived products—hence, enabling their activities in lipid signaling networks and cell homeostasis. Thus, understanding the DGK operational mode and interactions between the production and accumulation of PA would constitute a significant advancement in investigating the mechanism of stress adaptation in plants.
Alzheimer’s Disease (AD) is closely connected to aberrant lipid metabolism. However, how early AD-like pathology synchronously influences brain and plasma lipidome in AD mice remains unclear. The study of dynamic change of lipidome in early-stage AD mice could be of great interest for the discovery of lipid biomarkers for diagnosis and monitoring of early-stage AD. For the purpose, an untargeted lipidomic strategy was developed for the characterization of lipids (≤ 1,200 Da) perturbation occurring in plasma and brain in early-stage AD mice (2, 3 and 7 months) by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. Significant changes were detected in the levels of several lipid species including lysophospholipids, phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and Ceramides (Cers), as well as other related lipid compounds such as fatty acids (FAs), diacylglycerols (DGs) and triacylglycerols (TGs) in AD mice. In this sense, disorders of lipid metabolism appear to involve in multiple factors including overactivation of phospholipases and diacylglycerol lipases, decreased anabolism of lysophospholipids in plasma and PEs in plasma and brain, and imbalances in the levels of PCs, FAs and glycerides at different ages. We revealed the changing panels of potential lipid biomarkers with the development of early AD. The study raises the possibility of developing lipid biomarkers for diagnosis of early-stage AD.
Chilling injury is especially prominent in postharvest bananas stored at low temperature below 13 °C. To elucidate better the relationship between cell membrane lipids and chilling injury, an untargeted lipidomics approach using ultra-performance liquid chromatography–mass spectrometry was conducted. Banana fruit were stored at 6 °C for 0 (control) and 4 days and then sampled for lipid analysis. After 4 days of storage, banana peel exhibited a marked chilling injury symptom. Furthermore, 45 lipid compounds, including glycerophospholipids, saccharolipids, and glycerolipids, were identified with significant changes in peel tissues of bananas stored for 4 days compared with the control fruit. In addition, higher ratio of digalactosyldiacylglycerol (DGDG) to monogalactosyldiacylglycerol (MGDG) and higher levels of phosphatidic acid (PA) and saturated fatty acids but lower levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and unsaturated fatty acids were observed in banana fruit with chilling injury in contrast to the control fruit. Meanwhile, higher activities of phospholipase D (PLD) and lipoxygenase (LOX) were associated with significantly upregulated gene expressions of MaPLD1 and MaLOX2 and higher malondialdehyde (MDA) content in chilling injury-related bananas. In conclusion, our study indicated that membrane lipid degradation resulted from reduced PC and PE, but accumulated PA, while membrane lipid peroxidation resulted from the elevated saturation of fatty acids, resulting in membrane damage which subsequently accelerated the chilling injury occurrence of banana fruit during storage at low temperature.
Chilling and frost conditions impose major yield restraints to wheat crops in Australia and other temperate climate regions. Unpredictability and variability of field frost events are major impediments for cold tolerance breeding. Metabolome and lipidome profiling were used to compare the cold response in spikes of cold-tolerant Young and sensitive variety Wyalkatchem at the young microspore (YM) stage of pollen development. We aimed to identify metabolite markers that can reliably distinguish cold-tolerant and sensitive wheat varieties for future cold-tolerance phenotyping applications. We scored changes in spike metabolites and lipids for both varieties during cold acclimation after initial and prolonged exposure to combined chilling and freezing cycles (1 and 4 days, respectively) using controlled environment conditions. The two contrasting wheat varieties showed qualitative and quantitative differences in primary metabolites involved in osmoprotection, but differences in lipid accumulation most distinctively separated the cold response of the two wheat lines. These results resemble what we previously observed in flag leaves of the same two wheat varieties. The fact that this response occurs in tissue types with very different functions indicates that chilling and freezing tolerance in these wheat lines is associated with re-modelling of membrane lipid composition to maintain membrane fluidity.
This chapter intends to summarize the chemistry, biological activities, methods of identification and quantification, possible interactions, and industrial and pharmaceutical applications of plant lipids. Plant lipids are naturally occurring functional and structural components, which serve as permeable barrier to external environment of cells. The compositions and functions of plant lipids vary depending on the type of plant. However, lipids are complex structures; therefore, there are various ways to define and classify lipids. The plant lipids play major role in energy storage and signaling and include fatty acids (FA), triacylglycerols, phospholipids, waxes, galactolipids, sphingolipids, tocopherols and tocotrienols, carotenoids, sterols, fat-soluble vitamins, and other compounds. Different procedures of spectroscopy like ultraviolet visible (UV) spectroscopy, mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy along with liquid chromatography, paper chromatography, column chromatography, and gas chromatography are used to determine the structure of plant lipids molecules. The plant lipids vary in their occurrence, application, and utilization either as food, pharmaceutical, or other industries depending on their specific type. Moreover, the aim of this chapter is to compile the essential role and impact of plant lipids on human life and their application in different industries.
Purpose:
The purpose was to select a simple and reproducible method for lipid measurements of human tears with ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS). Two sample preparation procedures were evaluated and compared: the Bligh and Dyer (BD) liquid-liquid extraction method with chloroform and methanol and protein precipitation with isopropanol (IPA).
Methods:
Reproducibility and recovery efficiencies of 20 non-endogenous internal lipid standards were tested in 10-µl tear samples from healthy subjects. The lipid coverage and the simplicity of execution were also assessed. Lipid profiles of the tear extracts were acquired with UHPLC-MS, uhpland the lipids were identified using SimLipid software.
Results:
Both methods were robust producing good lipid coverage and reproducibility and high recovery efficiencies. The two protocols identified a 69-feature tear lipidome that covered 11 lipid classes from six different lipid categories. The main differences in recovery were due to the intrinsic lipid selectivity of each solvent. Although both methods were similarly efficient in recovering O-acyl-ω-hydroxy fatty acid (OAHFAs) and non-polar lipids, polar lipids were more efficiently recovered with IPA precipitation, which, in turn, exhibited higher reproducibility. In addition, IPA precipitation is automatable and simpler than the BD approach.
Conclusions:
IPA precipitation is an excellent procedure for extracting lipids from small tear volumes for quantitative large-scale, untargeted lipid profiling, which may be useful for identifying lipid biomarkers in tears from patients with different ocular surface pathologies, allowing personalized therapies to be designed.
Therapy‐induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro‐survival activity, we envisioned that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, we established a tissue culture model system and comparatively analyzed the cellular lipidomes of senescent and proliferating cells. Out of thousands of features detected, we identified 17 species that showed significant changes in senescent cells. The majority of these species (11 out of 17) were atypical sphingolipids, 1‐deoxyceramides/dihydroceramides which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids were depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide results in decreased senescence, suggesting that these species might play a key role in this process.
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