Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"Rapamycin induced autophagy enhances lipid breakdown and ameliorates lipotoxicity in Atlantic salmon cells","authors":"Kanchan Phadwal ,&nbsp;Jennifer Haggarty ,&nbsp;Dominic Kurian ,&nbsp;Judit Aguilar Martí ,&nbsp;Jianxuan Sun ,&nbsp;Ross D. Houston ,&nbsp;Mónica B. Betancor ,&nbsp;Vicky E. MacRae ,&nbsp;Phillip D. Whitfield ,&nbsp;Daniel J. Macqueen","doi":"10.1016/j.bbalip.2025.159636","DOIUrl":"10.1016/j.bbalip.2025.159636","url":null,"abstract":"<div><div>Autophagy is a highly conserved cellular recycling process essential for homeostasis in all eukaryotic cells. Lipid accumulation and its regulation by autophagy are key areas of research for understanding metabolic disorders in human and model mammals. However, the role of autophagy in lipid regulation remains poorly characterized in non-model fish species of importance to food production, which could be important for managing health and welfare in aquaculture. Addressing this knowledge gap, we investigate the role of autophagy in lipid regulation using a macrophage-like cell line (SHK-1) from Atlantic salmon (<em>Salmo salar</em> L.), the world's most commercially valuable farmed finfish. Multiple lines of experimental evidence reveal that the autophagic pathway responsible for lipid droplet breakdown is conserved in Atlantic salmon cells. We employed global lipidomics and proteomics analyses on SHK-1 cells subjected to lipid overload, followed by treatment with rapamycin to induce autophagy. This revealed that activating autophagy via rapamycin enhances storage of unsaturated triacylglycerols and suppresses key lipogenic proteins, including fatty acid elongase 6, fatty acid binding protein 2 and acid sphingomyelinase. Moreover, fatty acid elongase 6 and fatty acid binding protein 2 were identified as possible cargo for autophagosomes, suggesting a critical role for autophagy in lipid metabolism in fish. Together, this study establishes a novel model of lipotoxicity and advances understanding of lipid autophagy in fish cells, with significant implications for addressing fish health issues in aquaculture.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159636"},"PeriodicalIF":3.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHA suppresses hormone-sensitive and castration-resistant prostate cancer growth by decreasing de novo lipogenesis","authors":"G.H. Tamarindo ,&nbsp;C.F. Ribeiro ,&nbsp;S. Rodrigues ,&nbsp;R.M. Góes ,&nbsp;M. Loda","doi":"10.1016/j.bbalip.2025.159634","DOIUrl":"10.1016/j.bbalip.2025.159634","url":null,"abstract":"<div><h3>Objective</h3><div><em>De novo</em> lipogenesis (DNL) is associated with prostate cancer (PCa) progression, while fatty acid synthase (FASN) overexpression is a hallmark of DNL. Palmitate, its main product, is a saturated fatty acid that supports PCa growth. Polyunsaturated fatty acids (PUFAs), which can be acquired from the microenvironment, undergo peroxidation more readily and affect membrane fluidity. Docosahexaenoic acid (DHA) is a prototype PUFA omega-3 produced inefficiently in human cells. Its levels are low in PCa cells compared to normal cells. We hypothesize that excess DHA may reprogram lipid metabolism and induce cell growth suppression.</div></div><div><h3>Methods</h3><div>Androgen-responsive LNCaP, castration-resistant cells C4–2 and 22Rv1, human PCa castration-resistant organoids, and prostate cancer xenografts were exposed to DHA.</div></div><div><h3>Results</h3><div>DHA accumulated into lipid droplets as triacylglycerols and cholesterol esters, led to increased phospholipid acyl chain unsaturation and altered phospholipid ratio, a known trigger of endoplasmic reticulum (ER) stress. DHA caused a decrease in sterol regulatory element-binding protein (SREBP) transcriptional program, which, in turn, led to decreased expression of FASN. The subsequent reduction in DNL caused downregulation of the androgen receptor (AR) and its splice variant AR-V7. In addition, β-oxidation was enhanced, and DHA was preferentially oxidized over palmitate. Glucose oxidation also increased in the presence of DHA. Finally, DHA led to ROS overproduction, oxidative damage, and ER stress.</div></div><div><h3>Conclusions</h3><div>DHA reduces the growth of hormone-sensitive and castration-resistant PCa both <em>in vitro</em> and <em>in vivo via</em> deregulation of lipid metabolism.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159634"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lauric acid ameliorates excessive linoleic acid induced macrophage inflammatory response and oxidative stress in large yellow croaker (Larimichthys crocea)","authors":"Yuhang Tang ,&nbsp;Yanan Shen ,&nbsp;Wencong Lai ,&nbsp;Chuanwei Yao ,&nbsp;Changxu Sui ,&nbsp;Tingting Hao ,&nbsp;Jianlong Du ,&nbsp;Yueru Li ,&nbsp;Kangsen Mai ,&nbsp;Qinghui Ai","doi":"10.1016/j.bbalip.2025.159635","DOIUrl":"10.1016/j.bbalip.2025.159635","url":null,"abstract":"<div><div>Macrophages are particularly prone to inflammation and oxidative stress upon exogenous stimulus. Previous investigations have shown that lauric acid (LRA) exerts anti-inflammatory and antioxidant effects, however, the molecular mechanism remains elusive. This study aims to elucidate the function and molecular mechanisms by which LRA provided a defense against inflammation and oxidative stress brought by linoleic acid (LA), both <em>in vivo</em> and <em>in vitro</em>. Feeding trial results indicated that dietary LA led to severe inflammation and impaired antioxidant capacity in head kidney of large yellow croaker. The gene and protein expressions of inflammation-related were upregulated and those of antioxidant defense were down-regulated in the LA diet group, which were reversed by glycerol monolaurate (LRA derivative). Meanwhile, in macrophages, LRA suppressed the expressions of p-ERK and p-JNK and the gene expressions of pro-inflammatory factors induced by excessive LA. G protein coupled receptor 84 (GPR84, endogenous receptor of LRA) disturbance did not alter LRA-induced ERK and JNK MAPK pathways and pro-inflammatory gene expressions decline. Besides, LRA decreased reactive oxygen species (ROS) level and increased the expressions of nuclear factor erythroid 2-related factor 2 (NRF2). And blockage of NRF2 reversed the protective effect of LRA-mediated the protection against oxidative stress. Collectively, these results demonstrated that LRA attenuated LA-induced inflammation by suppressing ERK and JNK MAPK pathways and oxidative stress by activating NRF2 signaling in macrophages. These findings revealed that the function and molecular mechanisms of LRA alleviating inflammation and oxidative stress in macrophages, which provides new insights for enhancing immune cell function in vertebrates.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159635"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of asparagus (Asparagus officinalis L.) divinyl ether synthase (CYP74H2) catalysis by site-directed mutagenesis","authors":"Svetlana S. Gorina,&nbsp;Natalia V. Lantsova,&nbsp;Yana Y. Toporkova,&nbsp;Alexander N. Grechkin","doi":"10.1016/j.bbalip.2025.159633","DOIUrl":"10.1016/j.bbalip.2025.159633","url":null,"abstract":"<div><div>Divinyl ether synthases (DESs) are the enzymes catalyzing the dehydration of fatty acid hydroperoxides to divinyl ether oxylipins. DESs, along with allene oxide synthases (AOSs), hydroperoxide lyases (HPLs), and epoxyalcohol synthases (EASs), are members of the CYP74 clan of unusual cytochromes P450 playing a key role in the lipoxygenase pathway. The present work focuses on the study of the structure-function relationships in <em>Asparagus officinalis</em> DES (AoDES, CYP74H2) via site-directed mutagenesis at some catalytically essential sites. Single mutant forms L106F and L282G retained the DES activity. However, the L106F mutant possessed significant alteration of stereochemical specificity of divinyl ether synthesis compared with WT AoDES. For example, while WT AoDES specifically converted linoleic acid 13(<em>S</em>)-hydroperoxide into (11<em>Z</em>)-etheroleic acid, its yield was significantly reduced by the L106F mutation, whereas etheroleic and (all-<em>E</em>)-etheroleic acids were the major ones. In contrast, the L282G mutation did not significantly affect the (11<em>Z</em>)-etheroleic acid formation. However, the L282G protein produced some additional products like those of HPL and EAS, along with divinyl ethers. The L106F/L282G double mutant protein lost DES activity. It converted α-linolenic 9- and 13-hydroperoxides into HPL chain cleavage products. At the same time, this mutant efficiently converted the linoleic acid 9-hydroperoxide into diol, 9,14-dihydroxy-10,12-octadecadienoic acid, presumably via the hydrolysis of the short-lived epoxydiene, 9,10-epoxy-11,13-octadecadienoic acid. Furthermore, the L106F/L282G/Q343P triple mutant showed AOS activity alongside DES. The appearance of EAS and HPL catalysis, as well as the biosynthesis of 9,14-epoxydiene via short-lived epoxydiene via site-directed mutagenesis in the catalytically relevant domains of DES, was demonstrated for the first time.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159633"},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin receptor agonist AdipoRon regulates glucose and lipid metabolism via PPARγ signaling pathway in hepatocytes of large yellow croaker (Larimichthys crocea)","authors":"Xiang Xu,&nbsp;Xiao Tang,&nbsp;Renlei Ji,&nbsp;Xiaojun Xiang,&nbsp;Qiangde Liu,&nbsp;Shangzhe Han,&nbsp;Jianlong Du,&nbsp;Yueru Li,&nbsp;Kangsen Mai,&nbsp;Qinghui Ai","doi":"10.1016/j.bbalip.2025.159632","DOIUrl":"10.1016/j.bbalip.2025.159632","url":null,"abstract":"<div><div>Activation of adiponectin receptors (AdipoRs) has been shown to regulate glucose and lipid metabolism in mammalian hepatocytes. However, much less is known for their roles in fish. The current study demonstrated that AdipoRon, a small-molecule activator of AdipoRs, modulated glucose and lipid metabolism in large yellow croaker. In hepatocytes of large yellow croaker, AdipoRon upregulated the mRNA expression of <em>adipors</em> and <em>appl1</em>, while increasing phosphorylation levels of AMPK and AKT. These changes indicate the activation of AdipoR-mediated signaling. Furthermore, AdipoRon promoted glucose uptake, increased intracellular glucose content, as well as upregulated genes involved in glycogen synthesis and glycolysis whereas downregulated gluconeogenesis-related genes. On the other hand, AdipoRon facilitated free fatty acid (FFA) absorption by increasing the expression of fatty acid transport genes (<em>fat/cd36</em>, <em>fatp1</em>, and <em>fabp11</em>). It also enhanced triglyceride (TG) synthesis, evidenced by increased triglyceride levels and upregulation of <em>dgat2</em> and PPARγ, which is consistent with the effect of adiponectin (APN) in large yellow croaker. Additional evidence suggested that inhibition of PPARγ with GW9662 reduced the effects of AdipoRon on glucose uptake and lipid metabolism, indicating that PPARγ is a key mediator in these metabolic regulations. Overall, AdipoRon was found to modulate multiple metabolic processes in hepatocytes of large yellow croaker via PPARγ signaling pathway, and these findings suggested that AdipoRon might contribute to beneficial effects on metabolic homeostasis in teleosts.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159632"},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted lipidomic reveals dietary LA/n-3 PUFAs regulate inflammation and redox status via oxylipins in bivalves","authors":"Yuxiang Zhu ,&nbsp;Kai Liao ,&nbsp;Yang Liu ,&nbsp;Hailong Huang ,&nbsp;Yang Zhang ,&nbsp;Hui Ge ,&nbsp;Deshui Chen ,&nbsp;Bin Ma ,&nbsp;Jilin Xu","doi":"10.1016/j.bbalip.2025.159631","DOIUrl":"10.1016/j.bbalip.2025.159631","url":null,"abstract":"<div><div>Oxylipins are bioactive lipid mediators derived from fatty acids; however, a comprehensive investigation of oxylipin profiles is absent in bivalves. Moreover, the physiological functions and bioactivities of PUFA-derived oxylipins warrant further exploration. In this study, we found that appropriate dietary linoleic acid (LA)/n-3 PUFAs enhanced the growth of the clam <em>Sinonovacula constricta</em> and improved its survival under hydrogen peroxide (H₂O₂) stress. Targeted lipidomic showed that the high-LA diet increased accumulation of LA and LA-derived oxylipins. Interestingly, a similar pattern was observed for α-linolenic acid (ALA) and ALA-derived oxylipins, potentially contributing to the anti-inflammatory and antioxidant effects of this dietary pattern. However, dietary n-3 PUFAs provided greater protection against H₂O₂-induced damage. Dietary n-3 PUFAs significantly increased the levels of oxylipins derived from docosahexaenoic acid and eicosapentaenoic acid, particularly 14(<em>S</em>)-hydroxydocosahexaenoic acid (14(<em>S</em>)-HDHA) and 12-hydroxyeicosapentaenoic acid (12-HEPE). Furthermore, 14(<em>S</em>)-HDHA and 12-HEPE restored cell viability in hydrogen peroxide (H₂O₂)-treated RAW264.7 cells. Mechanistically, 12-HEPE inhibited nuclear factor kappa B (NF-κB) nuclear translocation while promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby reducing inflammatory responses and enhancing antioxidant capacity. Additionally, 12-HEPE increased antioxidant activity and suppressed inflammatory gene expression in clam hemolymph cells. This study represents the first comprehensive evaluation of the oxylipin profile in bivalves, further emphasizing the importance of dietary n-3 PUFAs intake in shaping n-3 PUFA-derived oxylipins and consequently influencing inflammation and redox status. Additionally, our study revealed that 12-HEPE alleviates cell damage induced by H₂O₂, with NF-κB and Nrf2 being key pathways.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159631"},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of perinatal supplementation of DHA on specialized pro-resolving lipid mediators in the brain of offspring","authors":"Stephanie Dubrof ,&nbsp;Jillien G. Zukaitis ,&nbsp;Ishfaque Ahmed ,&nbsp;Wenwu Sun ,&nbsp;Qun Zhao ,&nbsp;Hea Jin Park","doi":"10.1016/j.bbalip.2025.159629","DOIUrl":"10.1016/j.bbalip.2025.159629","url":null,"abstract":"<div><div>The perinatal period is crucial for fetal neurological development, relying on omega-3 polyunsaturated fatty acids (PUFAs) for essential processes. Omega-3 PUFA, including docosahexaenoic acid (DHA), are precursors to a novel class of bioactive metabolites called specialized pro-resolving mediators (SPMs), which have been suggested to have a dual purpose in mitigating neuroinflammation while simultaneously supporting cognitive outcomes, implicating a role in offspring neurodevelopment. DHA is evidenced for its role in early brain development, but the underlying mechanism it exerts its cognitive benefits remain unclear. Pregnant sows were fed a control diet (CON; <em>n</em> = 6) or a diet with DHA (<em>n</em> = 6, 75 mg DHA/kg BW/day) from gestation through lactation. At weaning, piglets (<em>n</em> = 2/sow) underwent resting state-functional magnetic resonance imaging (rs-fMRI) to assess brain functional activation. Subsequently, brain tissue from prefrontal cortex, cerebellum, and hippocampus were collected from piglets. Tissue DHA and eicosapentaenoic acid (EPA)-derived SPMs were quantified using LC-MS. Levels of SPMs were higher in the brains of piglets from DHA-fed sows, particularly in the prefrontal cortex and cerebellum, compared to control piglets. Additionally, a distinct association of several prefrontal SPMs with activation of the cerebellar functional network was marked in the piglet offspring. The findings highlight a potential for SPMs to function as mediators for neurodevelopmental programming, through contributing to inflammation resolution and neuronal connectivity. This work underscores the importance of maternal nutrition in shaping offspring brain health and lays the groundwork for targeted interventions leveraging the benefits of DHA and its bioactive metabolites.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159629"},"PeriodicalIF":3.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oroxylin A ameliorates non-alcoholic fatty liver disease by modulating oxidative stress and ferroptosis through the Nrf2 pathway","authors":"Yuzi Jiang,&nbsp;Kangwei Jiang,&nbsp;Peilin Sun,&nbsp;Yuan Liu,&nbsp;Hongming Nie","doi":"10.1016/j.bbalip.2025.159628","DOIUrl":"10.1016/j.bbalip.2025.159628","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a prevalent and progressive liver disorder posing a global health challenge. Oroxylin A, a naturally occurring flavonoid, with a broad spectrum of pharmacological activities. This study aimed to explore the therapeutic potential of oroxylin A and unravel its molecular mechanisms in mitigating high-fat diet (HFD)-induced NAFLD in murine models. Wild-type (WT) and nuclear factor erythroid 2-related factor 2 knockout (Nrf2^−/−) mice were administered a HFD to generate <em>in vivo</em> models, while free fatty acids-treated HepG2 cells served as the <em>in vitro</em> model. To investigate the effects of oroxylin A, serum and liver biochemical markers, hepatic histology, lipid metabolism, and oxidative stress were assessed in a NAFLD mouse model. The underlying mechanisms of oroxylin A were further explored through Western blotting, immunohistochemistry, and immunofluorescence analysis. Oroxylin A mitigated hepatic steatosis and injury by reducing liver index, AST, ALT, TG, and TC levels, improving histology, and restoring lipid metabolism. Glucose and insulin tolerance tests demonstrated improved glucose homeostasis and insulin sensitivity. Moreover, oroxylin A suppressed inflammation, apoptosis, and fibrosis, while enhancing antioxidant defenses, and improving mitochondrial function. Mechanistically, oroxylin A activated the Keap1/Nrf2/GPX4/SLC7A11 axis, upregulating Nrf2 and HO-1. These effects were abolished in Nrf2^−/− mice. <em>In vitro</em> results were consistent, and molecular docking, dynamics simulations, and CETSA confirmed its direct Keap1 binding. Oroxylin A protects against NAFLD by modulating the Nrf2 pathway, reducing oxidative stress and ferroptosis, making it a promising candidate for clinical NAFLD therapy.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159628"},"PeriodicalIF":3.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid desaturases in non-photosynthetic bacteria: classification, regulation, and roles in plasma membrane function and cellular homeostasis","authors":"Ye Tao ,&nbsp;Yilin Sun ,&nbsp;Yidan Chai ,&nbsp;Luminita Duma ,&nbsp;Yannick Rossez","doi":"10.1016/j.bbalip.2025.159630","DOIUrl":"10.1016/j.bbalip.2025.159630","url":null,"abstract":"<div><div>Fatty acid desaturases are key enzymes that catalyze the desaturation of acyl lipid chains by regioselectively introducing double bonds into saturated or pre-existing alkene fatty acids to produce unsaturated fatty acids. While extensive studies have focused on desaturases in higher organisms, research on these enzymes in non-photosynthetic bacteria remains limited, largely due to insufficient structural and functional data. This review aims to summarize the current knowledge on the structural features and catalytic mechanisms of desaturases in non-photosynthetic bacteria, shedding light on the sophisticated regulatory strategies underlying unsaturated fatty acid biosynthesis. In addition, factors influencing desaturase activity are presented and analyzed. This comprehensive review provides insights into bacterial homeostatic adaptation to environmental changes and highlights potential applications in nutraceutical development and therapeutic target identification.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159630"},"PeriodicalIF":3.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoinositide-specific phospholipase C enzymes: Recent advances in a long journey","authors":"Calum Macrae ,&nbsp;Damjan Lalović ,&nbsp;Tom D. Bunney,&nbsp;Matilda Katan","doi":"10.1016/j.bbalip.2025.159627","DOIUrl":"10.1016/j.bbalip.2025.159627","url":null,"abstract":"<div><div>A journey that started with the discovery of phospholipase C catalysed inositol-lipid hydrolysis as a receptor-controlled signalling event, culminated in defining molecular properties and roles of phosphoinositide-specific phospholipase C (PLC) families. Currently, there are six classical (13 isoforms) and one atypical (3 isoforms) family, expressed in a wide range of mammalian cells where they perform key functions in intracellular signal transduction. We here highlight recent advances in the PLC field, mostly resulting from studies of the PLCγ family members, PLCγ1 and PLCγ2. These new discoveries include elucidation of their structural and functional properties as well as their roles in physiology and disease development. We also illustrate the involvement of classical PLC families in control of cellular processes mediated not only by the PtdIns(4,5)<em>P</em>₂-derived second messengers, resulting from the PLC hydrolysis, but also by second messenger-independent consequences of PtdIns(4,5)<em>P</em>₂ hydrolysis. Presented examples are focused on regulation of ion channels by PtdIns(4,5)<em>P</em>₂.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159627"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}