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

{"title":"Specificity mechanism of Group VIA calcium-independent phospholipase A2 toward truncated-oxidized phospholipids and its application for specific inhibitor design","authors":"Daiki Hayashi ,&nbsp;Charikleia S. Batsika ,&nbsp;Asimina Bourboula ,&nbsp;Masakazu Shinohara ,&nbsp;Kengo Kanamaru ,&nbsp;George Kokotos ,&nbsp;Edward A. Dennis","doi":"10.1016/j.bbalip.2025.159655","DOIUrl":"10.1016/j.bbalip.2025.159655","url":null,"abstract":"<div><div>Phospholipase A₂ (PLA₂) constitutes a superfamily of enzymes that hydrolyze the <em>sn</em>-2 fatty acyl chain of glycerophospholipids. Polyunsaturated fatty acids (PUFAs) are preferentially attached at the <em>sn</em>-2 position of glycerophospholipids and are easily truncated by oxidation. The truncated-oxidized phospholipids (tr-oxPLs) trigger various cellular responses, and PLA₂s may play a critical role in the metabolism of the tr-oxPLs by removing the oxidized <em>sn</em>-2 chain. In the present study, we demonstrated using an in vitro lipidomics assay that Group VIA calcium-independent PLA₂ (GVIA iPLA₂) showed high activity toward phosphatidylcholine with a 9-oxononanoyl chain, but not with an azelaoyl chain on the <em>sn</em>-2 position. We conducted molecular dynamics simulations which revealed that the hydrophilicity of the <em>sn</em>-2 acyl chain critically affects the binding of the substrate in the active site. Based on the unique specificity of GVIA iPLA₂ toward tr-oxPLs, we synthesized an oxidatively modified inhibitor (GK766) for GVIA iPLA₂, aiming for improvement of its selectivity and/or potency. As we expected, the modified inhibitor improved its selectivity of GVIA iPLA₂ compared to the unmodified inhibitor (GK187), although the inhibitory effect became somewhat weaker. More importantly, we demonstrated that GK766 induces cell death by ferroptosis more effectively than GK187 using an erythroleukemia cell line. In the present study, we have further defined the unique substrate specificity of GVIA iPLA₂ toward tr-oxPLs and its molecular mechanism. Furthermore, we have developed a novel specificity-based inhibitor that induces ferroptosis demonstrating that using substrate selectivity helps in developing more effective therapeutics.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159655"},"PeriodicalIF":3.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537953","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":"Substrates, intermediates, and products of avian ketocarotenoid metabolism","authors":"Matthew B. Toomey ,&nbsp;Rebecca E. Koch ,&nbsp;Yu Liu ,&nbsp;Johannes von Lintig ,&nbsp;Joseph C. Corbo ,&nbsp;Geoffrey E. Hill ,&nbsp;Yufeng Zhang","doi":"10.1016/j.bbalip.2025.159654","DOIUrl":"10.1016/j.bbalip.2025.159654","url":null,"abstract":"<div><div>Carotenoid-based coloration is an essential feature of avian diversity and has important roles in communication and mate choice. The red feathers of birds from phylogenetically diverse orders and families are pigmented with C4-ketocarotenoids produced via the successive action of Cytochrome P450 2J19 (CYP2J19) and 3-hydroxybutyrate dehydrogenase 1-like (BDH1L) on yellow dietary precursors. Yet, the biochemistry of these enzymes remains incompletely understood. Here we present a series of experiments characterizing the substrates, intermediates, and products of CYP2J19 and BDH1L expressed in heterologous cell culture. We confirm that CYP2J19 preferentially hydroxylates the 4 and 4′ positions of β-ring substrates, but can also hydroxylate the 3 and 3 positions of C4-ketocarotenoids. We confirm that BDH1L catalyzes the conversion of zeaxanthin to canary xanthophyll B (ε,ε’-carotene-3,3′-dione) a major pigment in plumage of many yellow bird species. These results suggest that the actions of CYP2J19 and/or BDH1L can explain the presence of many metabolically transformed carotenoids in avian tissues.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159654"},"PeriodicalIF":3.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526338","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":"Carotenoid molecular actions in plants and animals","authors":"Hideki Hashimoto ,&nbsp;John W. Erdman Jr.","doi":"10.1016/j.bbalip.2025.159656","DOIUrl":"10.1016/j.bbalip.2025.159656","url":null,"abstract":"","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159656"},"PeriodicalIF":3.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526264","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":"Special issue entitled lipids in cancer biology by Marco Falasca","authors":"Marco Falasca","doi":"10.1016/j.bbalip.2025.159653","DOIUrl":"10.1016/j.bbalip.2025.159653","url":null,"abstract":"","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159653"},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493970","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":"PI(4,5)P2 is a master regulator for Ca2+-triggered vesicle exocytosis","authors":"Masaki Yamaga,&nbsp;Thomas F.J. Martin","doi":"10.1016/j.bbalip.2025.159651","DOIUrl":"10.1016/j.bbalip.2025.159651","url":null,"abstract":"<div><div>Substantial evidence indicates that phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P₂] is a plasma membrane phospholipid essential for Ca²⁺-dependent vesicle exocytosis. Ca²⁺-triggered vesicle exocytosis is a well-organized multiple-step membrane process including vesicle docking, priming, and soluble <em>N</em>-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent fusion. A subset of vesicles are docked on high concentration plasma membrane PI(4,5)P₂ microdomains that preferentially undergo exocytosis upon Ca²⁺-stimulation in neuroendocrine cells. PI(4,5)P₂ microdomains also mediate plasma membrane SNARE proteins syntaxin-1 and SNAP-25 partitioning and clustering through electrostatic interactions. PI(4,5)P₂ recruits and activates SNARE regulatory proteins such as calcium-dependent activator protein for secretion (CAPS, aka CADPS), mammalian uncoordinated-13 (Munc13), and synaptotagmin-1, which play pivotal roles in the priming and fusion steps of vesicle exocytosis. In this review, we discuss how PI(4,5)P₂ controls each step of vesicle exocytosis through PI(4,5)P₂-binding effector proteins.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159651"},"PeriodicalIF":3.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339880","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 phosphatases: Modifiers of phosphoinositide signaling in health and disease","authors":"Elizabeth M. Davies ,&nbsp;Emily I. Jones ,&nbsp;Lisa M. Ooms ,&nbsp;Rajendra Gurung ,&nbsp;Meagan J. McGrath ,&nbsp;Christina A. Mitchell","doi":"10.1016/j.bbalip.2025.159652","DOIUrl":"10.1016/j.bbalip.2025.159652","url":null,"abstract":"<div><div>Phosphoinositides are membrane-bound phospholipids that are derived from the reversible phosphorylation of phosphatidylinositol by the opposing actions of phosphoinositide kinases and phosphatases. Phosphoinositides are minor lipid constituents of cellular membranes; however, they assert a varied and profound influence on numerous biological processes both at the plasma membrane and on subcellular organelle membranes. Phosphoinositide phosphatases encompass multiple enzyme families that hydrolyze the phosphate group from the inositol ring of phosphoinositide species to modify signaling pathways that govern development and homeostasis. Genetic mutations that alter the function or expression of phosphoinositide phosphatases are causative of severe developmental syndromes or contribute to human diseases such as cancer, metabolic disorders and neuropathies. This review will focus on a select group of phosphoinositide phosphatase family members. Specifically, we will discuss the lipid and dual-specificity protein phosphatase PTEN, including the multiple regulatory mechanisms that define this enzyme as an established tumor suppressor. We will focus on recent discoveries that describe novel roles for phosphoinositide regulation on subcellular membranes by INPP5E and INPP5K, two members of the inositol polyphosphate 5-phosphatase family. Finally, the diverse biological and pathophysiological roles of the inositol polyphosphate 4-phosphatases, INPP4A and INPP4B, will be outlined. Collectively, these discussions will reveal the critical roles that phosphoinositide phosphatases play in both human development and for prevention of disease.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159652"},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339879","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":"Altered levels of sphingomyelins, ceramides, glycerophospholipids, and diacylglycerols in thymoma tissues","authors":"Jie Zhang ,&nbsp;Xiaoling Zang ,&nbsp;Wei Meng ,&nbsp;Peng Jiao ,&nbsp;Jiangyu Wu ,&nbsp;Lizhen Zhao ,&nbsp;Zhuangzhuang Li ,&nbsp;Xin Zhang ,&nbsp;Huanhuan Yang ,&nbsp;Zhihua Lv","doi":"10.1016/j.bbalip.2025.159650","DOIUrl":"10.1016/j.bbalip.2025.159650","url":null,"abstract":"<div><div>Thymoma is a rare thymic epithelial tumor, and its pathogenesis and lipid characteristics are still unclear. In this study, non-targeted lipidomics study by ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS) was conducted to analyze the alterations of lipids in 76 tissue samples from 24 thymoma, 14 thymic hyperplasia, and 1 thymic carcinoma (TC) patients. Sphingomyelins with 36–44 carbons (SM d36:1, SM d38:1, SM d40:1, SM d36:2, SM d38:2, SM d40:2, SM d41:2, SM d43:2, SM d44:2), medium, long and very-long chain ceramides (Cer d17:1/16:0, Cer d18:1/17:0, Cer d18:1/18:0, Cer d18:1/22:0, Cer d18:1/24:1, Cer d18:2/20:0, Cer d18:2/22:0), phosphatidylcholine (PC) 16:0_16:0, phosphatidylethanolamines (PE 16:0_16:0, PE 16:0_16:1, PE P-16:0_18:2), LPE 18:2, phosphatidylserine (PS) 18:1_22:0, diacylglycerols (DG 16:0_18:1 and DG 18:1_18:2) showed decreased levels, while polyunsaturated lysophosphatidylcholines (LPCs), PCs with long or very-long polyunsaturated acyl chains (PC 16:0_18:3, PC 18:0_22:5, PC 18:1_22:6, PC 15:0_18:2, PC 18:0_20:3, PC 18:0_20:4, PC 18:2_20:4, PC 20:2_20:4, PC 18:0_22:4, PC 20:4_22:4, PC O-18:0_20:4), part of identified PEs (PE P-16:0_18:1, PE P-18:0_20:4, PE P-16:0_22:6), DG 18:0_20:4, arachidyl carnitine, and 1-methylhistamine had increased levels in thymoma and 1 TC tissues compared to paired non-cancerous tissues. The most altered pathways in thymoma tissues were glycerophospholipid metabolism and sphingolipid metabolism. In addition, orthogonal partial least squares-discriminant analysis (oPLS-DA) based on 5 lipids (PC 18:0_20:3, PE 16:0_16:0, PC 18:0_22:5, PE P-16:0_18:1, and PC O-18:0_20:4) discriminated thymoma and 1 TC tissues from non-cancerous ones with 97.4 % accuracy, 100 % sensitivity, and 95.5 % specificity, showing a good discrimination ability.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159650"},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366631","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":"Cold-sensitive pathway elongates a non-native cis-7-hexadecenoic acid to cis-9-octadecenoic acid in the cyanobacterium Synechocystis sp. PCC 6803","authors":"Asuka Kobayashi ,&nbsp;Nattiwong Pankasem ,&nbsp;Kotaro Kobayashi ,&nbsp;Florence Corellou ,&nbsp;Kohei Yoneda ,&nbsp;Yoshiaki Maeda ,&nbsp;Iwane Suzuki","doi":"10.1016/j.bbalip.2025.159649","DOIUrl":"10.1016/j.bbalip.2025.159649","url":null,"abstract":"<div><div>Cellular membranes of the cyanobacterium <em>Synechocystis</em> sp. PCC 6803 primarily consist of glycerolipids esterified unsaturated C18 and saturated C16 fatty acids (FAs). We introduced the <em>Ot17.2</em> gene from the Mamiellophyceae <em>Ostreococcus tauri</em> into <em>Synechocystis</em>. The cells, <em>Ot17.2</em>+, produced <em>cis</em>-7-hexadecenoic acid (hypogeic acid, 16:1∆7) at the half level of the total C16 FAs, suggesting that the <em>Ot17.2</em> gene encodes chloroplast-localized C16-specific ∆7 desaturase. To study the effect of the synthesis of a non-native unsaturated C16 FA, we attempted to decrease the copy number of the <em>desC</em> gene for C18-specific ∆9 desaturase, producing <em>cis</em>-9-octadecenoic acid (oleic acid, 18:1∆9) in the <em>Ot17.2</em>+ strain. Surprisingly, the <em>desC</em> gene was entirely deleted in the <em>Ot17.2</em>+/<em>desC</em>- strain, despite the knowledge that the <em>desC</em> gene is essential for survival. We found that the C18 FAs in the strain were unsaturated as in the wild-type cells. In contrast, we could not delete the <em>desC</em> gene completely in the cells expressing the <em>desC2</em> gene for the C16 specific ∆9 desaturase, producing <em>cis</em>-9-hexadecenoic acid (palmitoleic acid, 16:1∆9). These findings indicate that <em>Synechocystis</em> may synthesize 18:1∆9 from 16:1∆7 via FA elongation, and <em>cis</em>-11-octade cenoic acid (vaccenic acid, 18:1∆11) produced from the elongation of 16:1∆9 may not sustain the cell growth. Interestingly, this strain (<em>Ot17.2</em>+/<em>desC</em>- strain) did not grow and produced little C18 unsaturated FAs at low temperatures. The supply of either 18:1∆9 or 16:1∆7 into the culture of <em>Ot17.2</em>+/<em>desC</em>- supported the growth, suggesting that the lipase activity involved in the FA salvage and elongation system might be severely sensitive to low temperatures.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159649"},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313432","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":"Adcy8 deficiency contributes to impaired lipolysis and an increased prevalence of obesity in mice","authors":"Mengxue Han ,&nbsp;Qing Shu ,&nbsp;Ruili Yu ,&nbsp;Shaohong Wu ,&nbsp;Handan Deng ,&nbsp;Yang Liu ,&nbsp;Quan Yu ,&nbsp;Wei Li ,&nbsp;Luyang Gao ,&nbsp;Yawen Zhao ,&nbsp;Geyang Xu","doi":"10.1016/j.bbalip.2025.159648","DOIUrl":"10.1016/j.bbalip.2025.159648","url":null,"abstract":"<div><div>Obesity is a global chronic disease characterized by an imbalance in energy homeostasis. Dysfunction of adipocytes and adipose tissue are fundamental defects that contribute to the development of obesity. Adenylate cyclase 8 (ADCY8) serves as a key downstream signaling factor of G protein-coupled receptors, catalyzing the conversion of ATP to cyclic AMP (cAMP), which is essential for maintaining energy balance. Although ADCY8 is expressed in adipose tissue, its specific role in adipose energy homeostasis remains unclear and warrants further investigation. Our findings demonstrate that compared to individuals with a normal body mass index (BMI), obese individuals exhibit increased visceral adipose tissue (VAT) accumulation, significantly enlarged adipocytes, reduced ADCY8 expression in VAT, decreased cAMP levels, and diminished phosphorylation of key lipolytic enzymes. In <em>Adcy8</em> knockout (<em>Adcy8</em>^{<em>−/−</em>}) mice, more severe lipid accumulation was observed under both normal and high-fat diet (HFD) conditions, accompanied by reduced activity of the adipose tissue cAMP-PKA signaling pathway. Notably, forskolin enhanced lipolysis and reduced adipocyte size in diet-induced obese wild-type mice, an effect abrogated in <em>Adcy8</em>^{<em>−/−</em>} mice. Collectively, these results indicate that adipose tissue ADCY8 regulates phosphorylation of lipolysis-related proteins via the cAMP-PKA signaling pathway, thereby influencing adipose tissue lipid accumulation. These findings establish ADCY8 as a novel molecular target and provide a theoretical foundation for obesity therapy.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159648"},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306469","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":"Hyperoxic recovery impacts on metabolic adaptations induced by hypoxic exercise: A lipidomics approach","authors":"Simone Serrao ,&nbsp;Eleonora Bossi ,&nbsp;Vanna Denti ,&nbsp;Johannes Burtscher ,&nbsp;Martin Faulhaber ,&nbsp;Günter Weiss ,&nbsp;Wolfgang Schobersberger ,&nbsp;Tobias Dünnwald ,&nbsp;Giuseppe Paglia","doi":"10.1016/j.bbalip.2025.159647","DOIUrl":"10.1016/j.bbalip.2025.159647","url":null,"abstract":"<div><div>This study investigates the effect of recovery phases in either hyperoxic air or hypoxic air during physical exercise in hypoxia on lipid metabolism in 11 male athletes.</div><div>We observed a long-term effect leading to increased plasma triacylglycerols and diacylglycerols, along with a decrease in sphingomyelin when athletes received supplemental oxygen during recovery. In contrast, no significant changes in circulating lipids were detected in athletes trained under hypoxic recovery conditions after 7 days.</div><div>We propose that hypoxic exercise induced potentially protective metabolic adaptations that might be disrupted by hyperoxic recovery.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159647"},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306468","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}