BiochimiePub Date : 2024-09-24DOI: 10.1016/j.biochi.2024.09.012
Delphine Vergoz, Annick Schaumann, Isabelle Schmitz, Maria van Agthoven, Sara Martí, Jordi Vila, Carlos Afonso, Emmanuelle Dé, Corinne Loutelier-Bourhis, Stéphane Alexandre
{"title":"Direct analysis by ultra-high-resolution mass spectrometry of lipid A and phospholipids from Acinetobacter baumannii cells.","authors":"Delphine Vergoz, Annick Schaumann, Isabelle Schmitz, Maria van Agthoven, Sara Martí, Jordi Vila, Carlos Afonso, Emmanuelle Dé, Corinne Loutelier-Bourhis, Stéphane Alexandre","doi":"10.1016/j.biochi.2024.09.012","DOIUrl":"10.1016/j.biochi.2024.09.012","url":null,"abstract":"<p><p>Acinetobacter baumannii, classified as priority number one by the World Health Organization (WHO), is an opportunistic pathogen responsible for infection and is able to develop antibiotic resistance easily. Membranes are bacteria's first line of defense against external aggression, such as antibiotics. A chemical modification of a lipid family or a change in lipid composition can lead to resistance to antibiotics. In this work, we analyzed different A. baumannii strains from various environments with different antibiotic resistance profiles, using matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS). This study shows that it is possible to describe the main lipidome (phospholipids and lipid A) from the simple preparation of lysed cells, and that despite the complexity of the mixture. This ultra-high resolution mass spectrometry technique enables the separation of isobaric ion, to report a new class of lipids. Given its performance, this technique can be used to quickly and reliably characterize the lipidome of clinical strains from different environments.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-23DOI: 10.1016/j.biochi.2024.09.010
Aneta Vrzalova, Radim Vrzal
{"title":"Orchestra of ligand-activated transcription factors in the molecular symphony of SERPINE 1 / PAI-1 gene regulation.","authors":"Aneta Vrzalova, Radim Vrzal","doi":"10.1016/j.biochi.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.09.010","url":null,"abstract":"<p><p>Plasminogen activator inhibitor 1 (PAI-1) is a crucial serine protease inhibitor that prevents plasminogen activation by inhibiting tissue- and urokinase-type plasminogen activators (tPA, uPA). PAI-1 is well-known for its role in modulating hemocoagulation or extracellular matrix formation by inhibiting plasmin or matrix metalloproteinases, respectively. PAI-1 is induced by pro-inflammatory cytokines across various tissues, yet its regulation by ligand-activated transcription factors is partly disregarded. Therefore, we have attempted to summarize the current knowledge on the transcriptional regulation of PAI-1 expression by the most relevant xenobiotic and endocrine receptors implicated in modulating PAI-1 levels. This review aims to contribute to the understanding of the specific, often tissue-dependent regulation of PAI-1 and provide insights into the modulation of PAI-1 levels beyond its direct inhibition.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracellular vesicles as a potential source of biomarkers for endocrine disruptors in MASLD: A short review on the case of DEHP.","authors":"Pierre-Etienne Merret, Lydie Sparfel, Catherine Lavau, Dominique Lagadic-Gossmann, Corinne Martin-Chouly","doi":"10.1016/j.biochi.2024.09.009","DOIUrl":"10.1016/j.biochi.2024.09.009","url":null,"abstract":"<p><p>Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is a chronic disease with increasing prevalence and for which non-invasive biomarkers are needed. Environmental endocrine disruptors (EDs) are known to be involved in the onset and progression of MASLD and assays to monitor their impact on the liver are being developed. Extracellular vesicles (EVs) mediate cell communication and their content reflects the pathophysiological state of the cells from which they are released. They can thus serve as biomarkers of the pathological state of the liver and of exposure to EDs. In this review, we present the relationships between DEHP (Di(2-ethylhexyl) phthalate) and MASLD and highlight the potential of EVs as biomarkers of DEHP exposure and the resulting progression of MASLD.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-21DOI: 10.1016/j.biochi.2024.09.011
G M Proshkina, E I Shramova, A B Mirkasyimov, O Yu Griaznova, E V Konovalova, A A Schulga, S M Deyev
{"title":"The Barnase-Barstar-based pre-targeting strategy for enhanced antitumor therapy in vivo.","authors":"G M Proshkina, E I Shramova, A B Mirkasyimov, O Yu Griaznova, E V Konovalova, A A Schulga, S M Deyev","doi":"10.1016/j.biochi.2024.09.011","DOIUrl":"10.1016/j.biochi.2024.09.011","url":null,"abstract":"<p><p>There is a great need for novel approaches to the treatment of epithelial ovarian carcinoma, which is the leading cause of mortality from gynecological malignancies. In this study, the pre-targeting technology was used to enhance the in vivo targeting of cytotoxic module composed of nanoliposomes loaded with a truncated form of Pseudomonas aeruginosa exotoxin A (PE40) to cancer cells. Pre-targeting system used in this study is composed of bacterial ribonuclease Barnase and its natural antitoxin Barstar. Barstar, genetically fused to various engineered scaffold proteins specific to tumor-associated antigens (HER2, EpCAM) serves as a primary module for precise cancer cell recognition. Barnase conjugated to a therapeutic agent serves as a cytotoxic or secondary module for malignant cell elimination. Due to strong non-covalent interaction (K<sub>D</sub>10<sup>-14</sup> M) of Barstar and Barnase, the primary and secondary modules efficiently interact with each other on the cell surface, which has been proven by confocal microscopy and flow cytometry. Using mice with SKOV-3 ovarian cancer xenografts, we have shown that regardless of the targeting module, the pre-targeting approach is much more effective than a single-step active targeting.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-19DOI: 10.1016/j.biochi.2024.09.007
Amazigh Hamaï, Guillaume Drin
{"title":"Specificity of lipid transfer proteins: An in vitro story.","authors":"Amazigh Hamaï, Guillaume Drin","doi":"10.1016/j.biochi.2024.09.007","DOIUrl":"10.1016/j.biochi.2024.09.007","url":null,"abstract":"<p><p>Lipids, which are highly diverse, are finely distributed between organelle membranes and the plasma membrane (PM) of eukaryotic cells. As a result, each compartment has its own lipid composition and molecular identity, which is essential for the functional fate of many proteins. This distribution of lipids depends on two main processes: lipid synthesis, which takes place in different subcellular regions, and the transfer of these lipids between and across membranes. This review will discuss the proteins that carry lipids throughout the cytosol, called LTPs (Lipid Transfer Proteins). More than the modes of action or biological roles of these proteins, we will focus on the in vitro strategies employed during the last 60 years to address a critical question: What are the lipid ligands of these LTPs? We will describe the extent to which these strategies, combined with structural data and investigations in cells, have made it possible to discover proteins, namely ORPs, Sec14, PITPs, STARDs, Ups/PRELIs, START-like, SMP-domain containing proteins, and bridge-like LTPs, which compose some of the main eukaryotic LTP families, and their lipid ligands. We will see how these approaches have played a central role in cell biology, showing that LTPs can connect distant metabolic branches, modulate the composition of cell membranes, and even create new subcellular compartments.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-18DOI: 10.1016/j.biochi.2024.09.005
Marita Vella, Iain W Manfield, Brandon C Seychell, Chi H Trinh, Robert Rambo, G Nasir Khan, Josanne Vassallo, Thérèse Hunter, Gary J Hunter
{"title":"Mutations in the N-domain of aryl hydrocarbon receptor interacting protein affect interactions with heat shock protein 90β and phosphodiesterase 4A5.","authors":"Marita Vella, Iain W Manfield, Brandon C Seychell, Chi H Trinh, Robert Rambo, G Nasir Khan, Josanne Vassallo, Thérèse Hunter, Gary J Hunter","doi":"10.1016/j.biochi.2024.09.005","DOIUrl":"10.1016/j.biochi.2024.09.005","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor interacting protein (AIP) is a cytoplasmic molecular co-chaperone and tumour suppressor that assists in protein stability and complex formation involving the aryl hydrocarbon receptor. Germline mutations in the AIP gene predispose to pituitary tumourigenesis with patients exhibiting an aggressive clinical phenotype. Full length AIP proteins harbouring N-domain mutations (R9Q, R16H, V49 M and K103R) were purified from E.coli utilizing a methodology that maintained structural integrity and monomeric stability. Mutations did not significantly affect the thermal stability of the protein and caused no overall disruptive effect in the protein structure. The mutations studied lowered the binding affinity of AIP towards two of its binding partners; heat shock protein 90β and phosphodiesterase 4A5 (PDE4A5). The inhibition of phosphodiesterase activity by AIP was also greatly reduced by all mutants. While previously published data has mainly concentrated on the tetratricopeptide repeats of the C-domain of AIP, we present clear evidence that AIP N-domain mutations play a significant role in two protein:protein interactions with partner proteins. The complex interactome of AIP suggests that any observable change in one or more of its binding partners cannot be disregarded as it may have repercussions on other biochemical pathways.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Established and emerging players in phospholipid scrambling: A structural perspective.","authors":"Heitor Gobbi Sebinelli, Camille Syska, Alenka Čopič, Guillaume Lenoir","doi":"10.1016/j.biochi.2024.09.008","DOIUrl":"10.1016/j.biochi.2024.09.008","url":null,"abstract":"<p><p>The maintenance of a diverse and non-homogeneous lipid composition in cell membranes is crucial for a multitude of cellular processes. One important example is transbilayer lipid asymmetry, which refers to a difference in lipid composition between the two leaflets of a cellular membrane. Transbilayer asymmetry is especially pronounced at the plasma membrane, where at resting state, negatively-charged phospholipids such as phosphatidylserine (PS) are almost exclusively restricted to the cytosolic leaflet, whereas sphingolipids are mostly found in the exoplasmic leaflet. Transbilayer movement of lipids is inherently slow, and for a fast cellular response, for example during apoptosis, transmembrane proteins termed scramblases facilitate the movement of polar/charged lipid headgroups through the membrane interior. In recent years, an expanding number of proteins from diverse families have been suggested to possess a lipid scramblase activity. Members of TMEM16 and XKR proteins have been implicated in blood clotting and apoptosis, whereas the scrambling activity of ATG9 and TMEM41B/VMP1 proteins contributes to the synthesis of autophagosomal membrane during autophagy. Structural studies, in vitro reconstitution of lipid scrambling, and molecular dynamics simulations have significantly advanced our understanding of the molecular mechanisms of lipid scrambling and helped delineate potential lipid transport pathways through the membrane. A number of examples also suggest that lipid scrambling activity can be combined with another activity, as is the case for TMEM16 proteins, which also function as ion channels, rhodopsin in the photoreceptor membrane, and possibly other G-protein coupled receptors.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-17DOI: 10.1016/j.biochi.2024.09.006
Chems Amari, Marta Carletti, Siqi Yan, Morgane Michaud, Juliette Salvaing
{"title":"Lipid droplets degradation mechanisms from microalgae to mammals, a comparative overview.","authors":"Chems Amari, Marta Carletti, Siqi Yan, Morgane Michaud, Juliette Salvaing","doi":"10.1016/j.biochi.2024.09.006","DOIUrl":"10.1016/j.biochi.2024.09.006","url":null,"abstract":"<p><p>Lipid droplets (LDs) are organelles composed of a hydrophobic core (mostly triacylglycerols and steryl esters) delineated by a lipid monolayer and found throughout the tree of life. LDs were seen for a long time as simple energy storage organelles but recent works highlighted their versatile roles in several fundamental cellular processes, particularly during stress response. LDs biogenesis occurs in the ER and their number and size can be dynamically regulated depending on their function, e.g. during development or stress. Understanding their biogenesis and degradation mechanisms is thus essential to better apprehend their roles. LDs degradation can occur in the cytosol by lipolysis or after their internalization into lytic compartments (e.g. vacuoles or lysosomes) using diverse mechanisms that depend on the considered organism, tissue, developmental stage or environmental condition. In this review, we summarize our current knowledge on the different LDs degradation pathways in several main phyla of model organisms, unicellular or pluricellular, photosynthetic or not (budding yeast, mammals, land plants and microalgae). We highlight the conservation of the main degradation pathways throughout evolution, but also the differences between organisms, or inside an organism between different organs. Finally, we discuss how this comparison can help to shed light on relationships between LDs degradation pathways and LDs functions.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-17DOI: 10.1016/j.biochi.2024.09.003
Khaled Tighanimine
{"title":"Lipid remodeling in context of cellular senescence.","authors":"Khaled Tighanimine","doi":"10.1016/j.biochi.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.09.003","url":null,"abstract":"<p><p>Cellular senescence is a response that irreversibly arrests stressed cells thus providing a potent tumor suppressor mechanism. In parallel, senescent cells exhibit an immunogenic secretome called SASP (senescence-associated secretory phenotype) that impairs tissue homeostasis and is involved in numerous age-related diseases. Senescence establishment is achieved through the unfolding of a profound transcriptional reprogramming together with morphological changes. These alterations are accompanied by important metabolic adaptations characterized by biosynthetic pathways reshuffling and lipid remodeling. In this mini-review we highlight the intricate links between lipid metabolism and the senescence program and we discuss the potential interventions on lipid pathways that can alleviate the senescence burden.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2024-09-14DOI: 10.1016/j.biochi.2024.09.004
Matthias Kühle, Joachim Kuhn, Thanh-Diep Ly, Cornelius Knabbe, Bastian Fischer
{"title":"Using targeted proteomics-based detection of collagen propeptides to quantify fibrillar collagen biogenesis in vitro.","authors":"Matthias Kühle, Joachim Kuhn, Thanh-Diep Ly, Cornelius Knabbe, Bastian Fischer","doi":"10.1016/j.biochi.2024.09.004","DOIUrl":"10.1016/j.biochi.2024.09.004","url":null,"abstract":"<p><p>The collagen superfamily, as the major structural component of the extracellular matrix, encompasses 28 distinct subtypes, with type-I and -III forming fibrils crucial for the matrix scaffold. During collagen biogenesis, trimers of type-I and -III procollagen are secreted into the extracellular matrix. The N- and C-terminal propeptides of these trimers are proteolytically cleaved from procollagen during secretion, initiating collagen fibril formation. The propeptides are released into extracellular space and, therefore, have been used to quantify collagen biogenesis. But high-throughput methods for the quantification of these biomarkers are still lacking. This study presents a state-of-the-art multiplexed approach for the simultaneous quantification of PINP, PICP, PIIINP and PIIICP from cell culture supernatants. The ability of targeted proteomics to quantify these propeptides from cell culture samples was assessed in this study. Using tryptic digestion and solid phase extraction, we were able to accurately quantify precollagen propeptides in a range of 3-1000 ng/mL. The assay showed an average inter-assay variance of 6.86 % with an overall recovery ranging from 92 to 98 %. The assay was validated using recombinant protein standards diluted in surrogate matrix and tested using transforming growth factor β1 mediated induction of normal human dermal fibroblasts. In summary, the assay presented in this paper offers a novel, robust, and precise high-throughput method for measuring human collagen propeptides in cell culture supernatants, empowering researchers to assess collagen biogenesis effectively in in vitro experiments.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}