Biochemical Journal最新文献_第6页

Retraction: Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155. 撤回：camp依赖性蛋白激酶对BAD的调节是通过一个新位点Ser155的磷酸化介导的。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-30 DOI: 10.1042/BJ3490547_RET

引用次数: 0

The C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination. n6 -甲基腺苷脱氨酶YerA的c端结构及其在脱氨中的作用。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-01-29 DOI: 10.1042/bcj20240728

Qian Jia,Hui Zeng,Nan Xiao,Jing Tang,Shangfang Gao,Wei Xie

{"title":"The C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination.","authors":"Qian Jia,Hui Zeng,Nan Xiao,Jing Tang,Shangfang Gao,Wei Xie","doi":"10.1042/bcj20240728","DOIUrl":"https://doi.org/10.1042/bcj20240728","url":null,"abstract":"The N6-methyladenine (6mA) modification is an essential epigenetic marker and plays a crucial role in processes, such as DNA repair, replication, gene expression regulation, etc. YerA from Bacillus subtilis is considered a novel class of enzymes capable of catalyzing the deamination of 6mA to produce hypoxanthine. Despite the significance of this type of enzymes in bacterial self-defense systems and potential applications as a gene-editing tool, the substrate specificity, the catalytic mechanism and the physiological function of YerA are currently unclear due to the lack of structural information. In this study, we expressed the recombinant enzyme and conducted its reconstitution to yield the active form. Our deamination assays showed that N6-methyladenosine (N6-mAdo) served as a more favorable substrate than its base derivative 6mA. Here we report the high-resolution structure of the C-terminal region of YerA, which exhibited a compact architecture composed of two antiparallel b-sheets with no obvious close structural homologs in PDB. We also created docking models to investigate the ligand-binding pattern, and found that more favorable contacts of N6-mAdo with the enzyme binding pocket lead to its preference for 6mA. Lastly, structural comparison to the deaminase MAPDA allowed us to propose a plausible role for this C-terminal region: shielding the active site from solvent and protecting the intermediate during catalysis. Taken together, this study sheds light on the catalytic mechanism and evolutionary pathways of the promiscuous enzyme YerA, thereby contributing to our molecular understanding of epigenetic nucleoside metabolism.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"79 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure, kinetics, and mechanism of Pseudomonas putida sulfoquinovose dehydrogenase, the first enzyme in the sulfoglycolytic Entner-Doudoroff pathway. 恶臭假单胞菌硫酸喹诺糖脱氢酶的结构、动力学和机制，这是硫解enner - doudoroff途径中的第一酶。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-01-22 DOI: 10.1042/bcj20240605

Laura Burchill,Mahima Sharma,Niccolay Madiedo Soler,Ethan D Goddard-Borger,Gideon J Davies,Spencer J Williams

{"title":"Structure, kinetics, and mechanism of Pseudomonas putida sulfoquinovose dehydrogenase, the first enzyme in the sulfoglycolytic Entner-Doudoroff pathway.","authors":"Laura Burchill,Mahima Sharma,Niccolay Madiedo Soler,Ethan D Goddard-Borger,Gideon J Davies,Spencer J Williams","doi":"10.1042/bcj20240605","DOIUrl":"https://doi.org/10.1042/bcj20240605","url":null,"abstract":"The sulfosugar sulfoquinovose (SQ) is catabolized through the sulfoglycolytic Entner-Doudoroff pathway, beginning with the oxidation of SQ to sulfogluconolactone by SQ dehydrogenase. We present a comprehensive structural and kinetic characterization of Pseudomonas putida SQ dehydrogenase (PpSQDH). PpSQDH is a tetrameric enzyme belonging to the short-chain dehydrogenase/reductase (SDR) superfamily with a strong preference for NAD+ over NADP+. Kinetic analysis revealed a rapid equilibrium ordered mechanism in which the NAD+ cofactor is the first substrate to bind, and NADH is the last product to dissociate. Structural studies revealed a homotetrameric structure in solution and crystals, involving cross-subunit interactions in which the C-terminus residue (Gln260) inserts into the diagonally opposite subunit to form part of the second shell of residues lining the active site. Complexes of PpSQDH with SQ or NAD+ provide insight into the recognition of SQ and together with the kinetic analysis allow the proposal of a catalytic reaction mechanism. Our findings illuminate the mechanism of SQ degradation and the evolution of the SDR superfamily for organosulfonate catabolism.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"20 1","pages":"57-72"},"PeriodicalIF":4.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins. 由物化原理决定的蛋白质淀粉样蛋白状态复杂多态性的结构共性。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-22 DOI: 10.1042/BCJ20240602

Silvia Errico, Giulia Fani, Salvador Ventura, Joost Schymkowitz, Frederic Rousseau, Antonio Trovato, Michele Vendruscolo, Francesco Bemporad, Fabrizio Chiti

{"title":"Structural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins.","authors":"Silvia Errico, Giulia Fani, Salvador Ventura, Joost Schymkowitz, Frederic Rousseau, Antonio Trovato, Michele Vendruscolo, Francesco Bemporad, Fabrizio Chiti","doi":"10.1042/BCJ20240602","DOIUrl":"10.1042/BCJ20240602","url":null,"abstract":"Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AAt) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer's disease, Parkinson's disease, and various tauopathies, respectively. This approach enabled a statistical analysis of sequences forming β-sheet regions in amyloid polymorphs. We computed for any given sequence residue n the fraction of PDB/AAt structures in which that residue adopts a β-sheet conformation (Fβ(n)) to generate an experimental, structure-based profile of Fβ(n) vs n, which represents the β-conformational preference of any residue in the amyloid state. The peaks in the respective Fβ(n) profiles of the three proteins, corresponding to sequence regions adopting more frequently the β-sheet structural core in the various fibrillar structures, align very well with the peaks identified with five predictive algorithms (ZYGGREGATOR, TANGO, PASTA, AGGRESCAN, and WALTZ). These results indicate that, despite amyloid polymorphism, sequence regions most often forming the structural core of amyloid have high hydrophobicity, high intrinsic β-sheet propensity and low electrostatic charge across the sequence, as rationalised and predicted by the algorithms.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"87-101"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nucleic acid joining enzymes: biological functions and synthetic applications beyond DNA. 核酸连接酶：DNA以外的生物功能和合成应用。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-22 DOI: 10.1042/BCJ20240136

Chelsea Blackstock, Caitlin Walters-Freke, Nigel Richards, Adele Williamson

{"title":"Nucleic acid joining enzymes: biological functions and synthetic applications beyond DNA.","authors":"Chelsea Blackstock, Caitlin Walters-Freke, Nigel Richards, Adele Williamson","doi":"10.1042/BCJ20240136","DOIUrl":"10.1042/BCJ20240136","url":null,"abstract":"DNA-joining by ligase and polymerase enzymes has provided the foundational tools for generating recombinant DNA and enabled the assembly of gene and genome-sized synthetic products. Xenobiotic nucleic acid (XNA) analogues of DNA and RNA with alternatives to the canonical bases, so-called 'unnatural' nucleobase pairs (UBP-XNAs), represent the next frontier of nucleic acid technologies, with applications as novel therapeutics and in engineering semi-synthetic biological organisms. To realise the full potential of UBP-XNAs, researchers require a suite of compatible enzymes for processing nucleic acids on a par with those already available for manipulating canonical DNA. In particular, enzymes able to join UBP-XNA will be essential for generating large assemblies and also hold promise in the synthesis of single-stranded oligonucleotides. Here, we review recent and emerging advances in the DNA-joining enzymes, DNA polymerases and DNA ligases, and describe their applications to UBP-XNA manipulation. We also discuss the future directions of this field which we consider will involve two-pronged approaches of enzyme biodiscovery for natural UBP-XNA compatible enzymes, coupled with improvement by structure-guided engineering.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 2","pages":"39-56"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury. 缺血再灌注后抑制 RIPK1 或 RIPK3 激酶活性可减少慢性肾损伤的发生。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-22 DOI: 10.1042/BCJ20240569

Aspasia Pefanis, Anjan K Bongoni, Jennifer L McRae, Evelyn J Salvaris, Nella Fisicaro, James M Murphy, Francesco L Ierino, Peter J Cowan

{"title":"Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury.","authors":"Aspasia Pefanis, Anjan K Bongoni, Jennifer L McRae, Evelyn J Salvaris, Nella Fisicaro, James M Murphy, Francesco L Ierino, Peter J Cowan","doi":"10.1042/BCJ20240569","DOIUrl":"10.1042/BCJ20240569","url":null,"abstract":"Ischemia-reperfusion injury (IRI) occurs when the blood supply to an organ is temporarily reduced and then restored. Kidney IRI is a form of acute kidney injury (AKI), which often progresses to kidney fibrosis. Necroptosis is a regulated necrosis pathway that has been implicated in kidney IRI. Necroptotic cell death involves the recruitment of the RIPK1 and RIPK3 kinases and the activation of the terminal effector, the mixed lineage kinase domain-like (MLKL) pseudokinase. Phosphorylated MLKL causes cell death by plasma membrane rupture, driving 'necroinflammation'. Owing to their apical role in the pathway, RIPK1 and RIPK3 have been implicated in the development of kidney fibrosis. Here, we used a mouse model of unilateral kidney IRI to assess whether the inhibition of RIPK1 or RIPK3 kinase activity reduces AKI and the progression to kidney fibrosis. Mice treated with the RIPK1 inhibitor Nec-1s, either before or after IR, showed reduced kidney injury at 24 hr compared with controls, whereas no protection was offered by the RIPK3 inhibitor GSK´872. In contrast, treatment with either inhibitor from days 3 to 9 post-IR reduced the degree of kidney fibrosis at day 28. These findings further support the role of necroptosis in IRI and provide important validation for the contribution of both RIPK1 and RIPK3 catalytic activities in the progression of kidney fibrosis. Targeting the necroptosis pathway could be a promising therapeutic strategy to mitigate kidney disease following IR.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"73-86"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico, in vitro and in vivo characterisation of thiamin binding proteins from plant seeds. 从植物种子中提取的硫胺素结合蛋白在体内和体外的特性。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-01-20 DOI: 10.1042/bcj20240429

Maria Faustino,Simon Strobbe,Raul Sanchez-Muñoz,Da Cao,Ratnesh C Mishra,Tiago Lourenço,Margarida Oliveira,Dominique Van Der Straeten

{"title":"In silico, in vitro and in vivo characterisation of thiamin binding proteins from plant seeds.","authors":"Maria Faustino,Simon Strobbe,Raul Sanchez-Muñoz,Da Cao,Ratnesh C Mishra,Tiago Lourenço,Margarida Oliveira,Dominique Van Der Straeten","doi":"10.1042/bcj20240429","DOIUrl":"https://doi.org/10.1042/bcj20240429","url":null,"abstract":"Thiamin, an essential micronutrient, is a cofactor for enzymes involved in the central carbon metabolism and amino acids pathways. Despite efforts to enhance thiamin content in rice by incorporating thiamin biosynthetic genes, increasing thiamin content in endosperm remains challenging, possibly due to a lack of thiamin stability and/or a local sink. The introduction of storage proteins has been successful in biofortification strategies and similar efforts targeting thiamin led to a 3-4-fold increase in white rice. However, only one thiamin-binding protein (TBP) sequence has been described in plants, more specifically from sesame seeds. Therefore, we aimed to identify and characterize TBPs, as well as to evaluate the effect of their expression on thiamin concentration, using an approach integrating in silico, in vitro and in vivo methods. We identified putative TBPs from Oryza sativa (rice), Fagopyrum esculentum (buckwheat) and Zea mays (maize) and pinpointed the thiamin-binding pockets through molecular docking. FeTBP and OsTBP contained one pocket with binding affinities similar to E. coli TBP, a well-characterized thiamin-binding protein, supporting their function. In vivo expression studies of TBPs in tobacco leaves and rice callus resulted in increased thiamin levels, with FeTBP and OsTBP showing the most pronounced effects. Additionally, thermal shift assays confirmed the thiamin binding capabilities of FeTBP and OsTBP, as observed by the significant increases in melting temperatures upon thiamin binding, indicating protein stabilization. These findings offer new insights into diversity and function of plant TBPs and highlight the potential of FeTBP and OsTBP to modulate thiamin levels in crop plants.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"24 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Specialized killing across the domains of life by the type VI secretion systems of Pseudomonas aeruginosa. 通过铜绿假单胞菌的VI型分泌系统在生命的各个领域进行专门杀伤。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-08 DOI: 10.1042/BCJ20230240

Jake Colautti, Steven D Kelly, John C Whitney

{"title":"Specialized killing across the domains of life by the type VI secretion systems of Pseudomonas aeruginosa.","authors":"Jake Colautti, Steven D Kelly, John C Whitney","doi":"10.1042/BCJ20230240","DOIUrl":"10.1042/BCJ20230240","url":null,"abstract":"Type VI secretion systems (T6SSs) are widespread bacterial protein secretion machines that inject toxic effector proteins into nearby cells, thus facilitating both bacterial competition and virulence. Pseudomonas aeruginosa encodes three evolutionarily distinct T6SSs that each export a unique repertoire of effectors. Owing to its genetic tractability, P. aeruginosa has served as a model organism for molecular studies of the T6SS. However, P. aeruginosa is also an opportunistic pathogen and ubiquitous environmental organism that thrives in a wide range of habitats. Consequently, studies of its T6SSs have provided insight into the role these systems play in the diverse lifestyles of this species. In this review, we discuss recent advances in understanding the regulation and toxin repertoire of each of the three P. aeruginosa T6SSs. We argue that these T6SSs serve distinct physiological functions; whereas one system is a dedicated defensive weapon for interbacterial antagonism, the other two T6SSs appear to function primarily during infection. We find support for this model in examining the signalling pathways that control the expression of each T6SS and co-ordinate the activity of these systems with other P. aeruginosa behaviours. Furthermore, we discuss the effector repertoires of each T6SS and connect the mechanisms by which these effectors kill target cells to the ecological conditions under which their respective systems are activated. Understanding the T6SSs of P. aeruginosa in the context of this organism's diverse lifestyles will provide insight into the physiological roles these secretion systems play in this remarkably adaptable bacterium.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 1","pages":"1-15"},"PeriodicalIF":4.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes. MYO1B和MYO5B运动蛋白以及分选连接蛋白SNX27调控肠细胞中膜黏液蛋白MUC17的顶端靶向。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-08 DOI: 10.1042/BCJ20240204

Sofia Jäverfelt, Gustaf Hellsén, Izumi Kaji, James R Goldenring, Thaher Pelaseyed

{"title":"The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes.","authors":"Sofia Jäverfelt, Gustaf Hellsén, Izumi Kaji, James R Goldenring, Thaher Pelaseyed","doi":"10.1042/BCJ20240204","DOIUrl":"10.1042/BCJ20240204","url":null,"abstract":"A dense glycocalyx, composed of the megaDalton-sized membrane mucin MUC17, coats the microvilli in the apical brush border of transporting intestinal epithelial cells, called enterocytes. The formation of the MUC17-based glycocalyx in the mouse small intestine occurs at the critical suckling-weaning transition. The glycocalyx extends 1 µm into the intestinal lumen and prevents the gut bacteria from directly attaching to the enterocytes. To date, the mechanism behind the positioning of MUC17 to the brush border is not known. Here, we show that the actin-based motor proteins MYO1B and MYO5B, and the sorting nexin SNX27, regulate apical targeting of MUC17 in enterocytes. We demonstrate that MUC17 turnover at the brush border is slow and controlled by MYO1B and SNX27. Furthermore, we report that MYO1B regulates MUC17 protein levels in enterocytes, whereas MYO5B specifically governs MUC17 levels at the brush border. Together, our results extend our understanding of the apical targeting of membrane mucins and provide mechanistic insights into how defective positioning of MUC17 renders enterocytes sensitive to bacterial challenges.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1-23"},"PeriodicalIF":4.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of peroxiredoxin 6 alters lipid composition and distribution resulting in increased sensitivity to ferroptosis. 过氧化物歧化酶 6 (PRDX6) 的缺失会改变脂质的组成和分布，从而增加对铁中毒的敏感性。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-23 DOI: 10.1042/BCJ20240445

Daniel J Lagal, Ángel Ortiz-Alcántara, José R Pedrajas, Brian McDonagh, J Antonio Bárcena, Raquel Requejo-Aguilar, C Alicia Padilla

{"title":"Loss of peroxiredoxin 6 alters lipid composition and distribution resulting in increased sensitivity to ferroptosis.","authors":"Daniel J Lagal, Ángel Ortiz-Alcántara, José R Pedrajas, Brian McDonagh, J Antonio Bárcena, Raquel Requejo-Aguilar, C Alicia Padilla","doi":"10.1042/BCJ20240445","DOIUrl":"10.1042/BCJ20240445","url":null,"abstract":"Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme involved in phospholipid peroxide repair and metabolism. In this study we investigated the global lipid composition of a human hepatocarcinoma cell line SNU475 lacking PRDX6 and lipid related cellular processes. There was a general decrease in multiple lipids species upon loss of PRDX6, in particular sphingomyelins and acylcarnitines, consistent with previously observed alterations in cell signaling pathways and mitochondrial dysfunction. Deprivation of docosahexaenoic acid and related species was also evident. However, a few striking exceptions are worth highlighting: (1) Three specific arachidonic acid (AA) containing phophatidylcholines (PC) increased significantly. The increase of sn1-stearic/sn2-PUFA containing PC and sn2-AA containing plasmenyls are indicative of a preference of PRDX6 iPLA2 activity for these AA storage glycerophospholipids. (2) Several polyunsaturated fatty acids (PUFA) and PUFA containing triacylglycerols accumulated together with increased formation of lipid droplets, an indication of altered FA flux and PUFA sequestration in PRDX6 knockout cells. Loss of PRDX6 resulted in increased sensitivity to erastin-induced ferroptosis, independent of selenium and GPX4, as a consequence of increased levels of lipid hydroperoxides, that reverted to normal levels upon rescue with PRDX6. The results presented demonstrate that all three enzymatic activities of PRDX6 contribute to the role of this multifunctional enzyme in diverse cellular processes, including membrane phospholipid remodeling and glycerophospholipid functional diversity, resulting in altered lipid peroxides and modulation of AA disposition and traffic. These contributions highlight the complexity of the changes that loss of PRDX6 exerts on cell functionality.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1997-2015"},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0