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The antibacterial activity and mechanisms of Trp-containing peptides against multidrug-resistant Pseudomonas aeruginosa persisters 含 Trp 肽对耐多药铜绿假单胞菌宿主的抗菌活性和机制。
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-29 DOI: 10.1016/j.biochi.2024.05.019
Mengmiao Li , Xiaomi Sun , Lei Zhao , Wanying Du , Dejing Shang
{"title":"The antibacterial activity and mechanisms of Trp-containing peptides against multidrug-resistant Pseudomonas aeruginosa persisters","authors":"Mengmiao Li ,&nbsp;Xiaomi Sun ,&nbsp;Lei Zhao ,&nbsp;Wanying Du ,&nbsp;Dejing Shang","doi":"10.1016/j.biochi.2024.05.019","DOIUrl":"10.1016/j.biochi.2024.05.019","url":null,"abstract":"<div><p>Bacterial persisters avoid antibiotic-mediated death by entering a dormant state and are considered a major cause of antibiotic treatment failure. Antimicrobial peptides (AMPs) with membrane-disrupting activity are promising drugs to eradicate persister cells. In this study, carbonyl cyanide m-chlorophenylhydrazone (CCCP), ciprofloxacin (CIP), and rifampicin (RFP) were applied to induce the formation of multidrug-resistant <em>Pseudomonas aeruginosa</em> (MRPA0108) persisters, and the antibacterial activity and mechanisms of I1W and L12W (two Trp-containing peptides designed in our lab) against MRPA0108 persisters were investigated. The results showed that I1W and L12W displayed potent antibacterial activity against MRPA0108 persisters. Both Trp-containing peptides disturbed the inner and outer membrane of MRPA0108 persisters. In addition, I1W and L12W revealed novel antibacterial mechanisms by decreasing the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT), increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, consequently leading to oxidative stress. The transcriptome profile of I1W-treated MRPA0108 persisters revealed that the genes involved in carbon metabolism, biosynthesis of amino acids, and the TCA cycle were downregulated, indicating that I1W interfered with metabolism and energy synthesis processes. Furthermore, both Trp-containing peptides displayed synergistic activities with antibiotic tobramycin and showed additive activities with cefepime or ciprofloxacin, which revealed a potential therapeutic strategy for the eradication of MRPA0108 persisters.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 133-145"},"PeriodicalIF":3.9,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181685","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
Hypoxia-induced downregulation of RNA m6A protein machinery in the naked mole-rat heart 缺氧诱导的裸鼹鼠心脏 RNA m6A 蛋白机制下调
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-22 DOI: 10.1016/j.biochi.2024.05.017
W. Aline Ingelson-Filpula , Karen L. Kadamani , Mohammad Ojaghi , Matthew E. Pamenter , Kenneth B. Storey
{"title":"Hypoxia-induced downregulation of RNA m6A protein machinery in the naked mole-rat heart","authors":"W. Aline Ingelson-Filpula ,&nbsp;Karen L. Kadamani ,&nbsp;Mohammad Ojaghi ,&nbsp;Matthew E. Pamenter ,&nbsp;Kenneth B. Storey","doi":"10.1016/j.biochi.2024.05.017","DOIUrl":"10.1016/j.biochi.2024.05.017","url":null,"abstract":"<div><p>Naked mole-rats, <em>Heterocephalus glaber</em>, are champion hypoxia-tolerant rodents that live under low oxygen conditions in their subterranean burrows. Detrimental effects of low oxygen can be mitigated through metabolic rate depression (MRD), metabolic reorganization, and global downregulation of nonessential cellular processes. Recent research has progressively implicated epigenetic modifications – rapid, reversible changes to gene expression that do not alter the DNA sequence itself – as major players in implementing and maintaining MRD. N<sup>6</sup>-adenosine (m<sup>6</sup>A) methylation is the most prevalent mammalian RNA modification and is responsible for pre-mRNA processing and mRNA export from the nucleus. Hence, m<sup>6</sup>A -mediated conformational changes alter the cellular fate of transcripts. The present study investigated the role of m<sup>6</sup>A RNA methylation responses to 24 h of hypoxia exposure in <em>H. glaber</em> cardiac tissue. Total protein levels of m<sup>6</sup>A writers/readers/erasers, m<sup>6</sup>A demethylase activity, and total m<sup>6</sup>A quantification were measured under normoxic vs. hypoxic conditions in <em>H. glaber</em> heart. While there was no change in either demethylase activity or total m<sup>6</sup>A content, many proteins of the m<sup>6</sup>A pathway were downregulated during hypoxia. Overall, m<sup>6</sup>A may not be a signature hypoxia-responsive characteristic in <em>H. glaber</em> heart, but downregulation of the protein machinery involved in m<sup>6</sup>A cycling points to an alternate biological involvement. Further research will explore other forms of RNA modifications and other epigenetic mechanisms to determine the controls on hypoxia endurance in this subterranean mammal.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 125-132"},"PeriodicalIF":3.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001196/pdfft?md5=e4516dd4a25e746db6a4198b7ec50cc9&pid=1-s2.0-S0300908424001196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094807","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
Structure-based drug design for TSPO: Challenges and opportunities 针对 TSPO 的基于结构的药物设计:挑战与机遇。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-05-22 DOI: 10.1016/j.biochi.2024.05.018
{"title":"Structure-based drug design for TSPO: Challenges and opportunities","authors":"","doi":"10.1016/j.biochi.2024.05.018","DOIUrl":"10.1016/j.biochi.2024.05.018","url":null,"abstract":"<div><p>The translocator protein 18 kDa (TSPO) is an evolutionarily conserved mitochondrial transmembrane protein implicated in various neuropathologies and inflammatory conditions, making it a longstanding diagnostic and therapeutic target of interest. Despite the development of various classes of TSPO ligand chemotypes, and the elucidation of bacterial and non-human mammalian experimental structures, many unknowns exist surrounding its differential structural and functional features in health and disease. There are several limitations associated with currently used computational methodologies for modelling the native structure and ligand-binding behaviour of this enigmatic protein. In this perspective, we provide a critical analysis of the developments in the uses of these methods, outlining their uses, inherent limitations, and continuing challenges. We offer suggestions of unexplored opportunities that exist in the use of computational methodologies which offer promise for enhancing our understanding of the TSPO.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"224 ","pages":"Pages 41-50"},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001202/pdfft?md5=5861fa0167f6689f46ed0ac5bc6ac94d&pid=1-s2.0-S0300908424001202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089230","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
Inside front cover-EDB 封面内页-EDB
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-21 DOI: 10.1016/S0300-9084(24)00109-3
{"title":"Inside front cover-EDB","authors":"","doi":"10.1016/S0300-9084(24)00109-3","DOIUrl":"https://doi.org/10.1016/S0300-9084(24)00109-3","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":"Page IFC"},"PeriodicalIF":3.9,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001093/pdfft?md5=f3e0bfe0b632556a31ed361b72f9347c&pid=1-s2.0-S0300908424001093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077870","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
A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing FSTL1 的特异位点磷酸化决定了它在伤口愈合中的促进作用。
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-19 DOI: 10.1016/j.biochi.2024.05.016
Anagha Priya Suresh , Monisha Vijayarengan , Pooja Aggarwal , Rajendran Soundaram , B.S. Gnanesh Kumar , Gopinath M. Sundaram
{"title":"A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing","authors":"Anagha Priya Suresh ,&nbsp;Monisha Vijayarengan ,&nbsp;Pooja Aggarwal ,&nbsp;Rajendran Soundaram ,&nbsp;B.S. Gnanesh Kumar ,&nbsp;Gopinath M. Sundaram","doi":"10.1016/j.biochi.2024.05.016","DOIUrl":"10.1016/j.biochi.2024.05.016","url":null,"abstract":"<div><p>Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using <em>in-silico</em> analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 <em>in vitro</em>. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely <em>via</em> its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, <em>trans</em>-dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 106-113"},"PeriodicalIF":3.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072356","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
Exploring venom diversity in Mixcoatlus browni and Mixcoatlus barbouri: A comparative analysis of two rare Mexican snake species with crotoxin-like presence Exploring Venom Diversity in Mixcoatlus browni and Mixcoatlus barbouri:两种含有类似克罗毒素的墨西哥稀有蛇类的比较分析。
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-16 DOI: 10.1016/j.biochi.2024.05.015
Edgar Neri-Castro , Vanessa Zarzosa , Bruno Lomonte , Fernando Zamudio , Lorena Hernandez-Orihuela , Alejandro Olvera-Rodríguez , Audrey Michelle Rodríguez-Solís , Miguel Borja , Uri O. García-Vázquez , Jason M. Jones , Chistopher L. Parkinson , Alejandro Alagón
{"title":"Exploring venom diversity in Mixcoatlus browni and Mixcoatlus barbouri: A comparative analysis of two rare Mexican snake species with crotoxin-like presence","authors":"Edgar Neri-Castro ,&nbsp;Vanessa Zarzosa ,&nbsp;Bruno Lomonte ,&nbsp;Fernando Zamudio ,&nbsp;Lorena Hernandez-Orihuela ,&nbsp;Alejandro Olvera-Rodríguez ,&nbsp;Audrey Michelle Rodríguez-Solís ,&nbsp;Miguel Borja ,&nbsp;Uri O. García-Vázquez ,&nbsp;Jason M. Jones ,&nbsp;Chistopher L. Parkinson ,&nbsp;Alejandro Alagón","doi":"10.1016/j.biochi.2024.05.015","DOIUrl":"10.1016/j.biochi.2024.05.015","url":null,"abstract":"<div><p>The genus <em>Mixcoatlus</em> is composed of three species: <em>Mixcoatlus barbouri</em>, <em>M. browni</em>, and <em>M. melanurus</em>, of which the venom composition of <em>M. melanurus</em>, the most common species of the three, has only recently been described. However, very little is known about the natural history of <em>M. barbouri</em> and <em>M. browni</em>, and the venom composition of these two species has remained thus far unexplored. In this study we characterize the proteomic profiles and the main biochemical and toxic activities of these two venoms. Proteomic data obtained by shotgun analysis of whole venom identified 12 protein families for <em>M. barbouri</em>, and 13 for <em>M</em>. <em>browni</em>. The latter venom was further characterized by using a quantitative ‘venomics’ protocol, which revealed that it is mainly composed of 51.1 % phospholipases A<sub>2</sub> (PLA<sub>2</sub>), 25.5 % snake venom serine proteases (SVSP), 4.6 % <span>l</span>-amino oxidases (LAO), and 3.6 % snake venom metalloproteases (SVMP), with lower percentages other six protein families. Both venoms contained homologs of the basic and acidic subunits of crotoxin. However, due to limitations in <em>M. barbouri</em> venom availability, we could only characterize the crotoxin-like protein of <em>M. browni</em> venom, which we have named Mixcoatlutoxin. It exhibited a lethal potency in mice like that described for classical rattlesnake crotoxins. These findings expand knowledge on the distribution of crotoxin-like heterodimeric proteins in viper snake species. Further investigation of the bioactivities of the venom of <em>M. barbouri</em>, on the other hand, remains necessary.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 81-88"},"PeriodicalIF":3.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960865","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
Highly specific aptamer trap for extremophilic RNA polymerases 针对嗜极 RNA 聚合酶的高特异性适配体陷阱。
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-16 DOI: 10.1016/j.biochi.2024.05.014
Ivan Petushkov , Andrey Feklistov , Andrey Kulbachinskiy
{"title":"Highly specific aptamer trap for extremophilic RNA polymerases","authors":"Ivan Petushkov ,&nbsp;Andrey Feklistov ,&nbsp;Andrey Kulbachinskiy","doi":"10.1016/j.biochi.2024.05.014","DOIUrl":"10.1016/j.biochi.2024.05.014","url":null,"abstract":"<div><p>During transcription initiation, the holoenzyme of bacterial RNA polymerase (RNAP) specifically recognizes promoters using a dedicated σ factor. During transcription elongation, the core enzyme of RNAP interacts with nucleic acids mainly nonspecifically, by stably locking the DNA template and RNA transcript inside the main cleft. Here, we present a synthetic DNA aptamer that is specifically recognized by both core and holoenzyme RNAPs from extremophilic bacteria of the <em>Deinococcus-Thermus</em> phylum. The aptamer binds RNAP with subnanomolar affinities, forming extremely stable complexes even at high ionic strength conditions, blocks RNAP interactions with the DNA template and inhibits RNAP activity during transcription elongation. We propose that the aptamer binds at a conserved site within the downstream DNA-binding cleft of RNAP and traps it in an inactive conformation. The aptamer can potentially be used for structural studies to reveal RNAP conformational states, affinity binding of RNAP and associated factors, and screening of transcriptional inhibitors.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 99-105"},"PeriodicalIF":3.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047561","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 evidence that substitution of glycine for valine (p.G8V) in a common variant of TMPRSS2 isoform 1 increases accessibility to an endocytic signal: Implication for SARS-cov-2 entry into host cells and susceptibility to COVID-19 硅学证据表明,在 TMPRSS2 同工酶 1 的一个常见变体中用甘氨酸取代缬氨酸(p.G8V)增加了内细胞信号的可及性:这与 SARS-CoV-2 进入宿主细胞和对 COVID-19 的易感性有关。
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-14 DOI: 10.1016/j.biochi.2024.05.004
Matteo Calcagnile , Fabrizio Damiano , Giambattista Lobreglio , Luisa Siculella , Maria Pia Bozzetti , Patricia Forgez , Alexandra Malgoyre , Nicolas Libert , Cecilia Bucci , Marco Alifano , Pietro Alifano
{"title":"In silico evidence that substitution of glycine for valine (p.G8V) in a common variant of TMPRSS2 isoform 1 increases accessibility to an endocytic signal: Implication for SARS-cov-2 entry into host cells and susceptibility to COVID-19","authors":"Matteo Calcagnile ,&nbsp;Fabrizio Damiano ,&nbsp;Giambattista Lobreglio ,&nbsp;Luisa Siculella ,&nbsp;Maria Pia Bozzetti ,&nbsp;Patricia Forgez ,&nbsp;Alexandra Malgoyre ,&nbsp;Nicolas Libert ,&nbsp;Cecilia Bucci ,&nbsp;Marco Alifano ,&nbsp;Pietro Alifano","doi":"10.1016/j.biochi.2024.05.004","DOIUrl":"10.1016/j.biochi.2024.05.004","url":null,"abstract":"<div><p>The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The <em>TMPRSS2</em> gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G &gt; T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the <em>TMPRSS2</em>-c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p &lt; 0.05) when the genotype data (<em>TMPRSS2</em>-c.23T/c.23T homozygotes + <em>TMPRSS2</em>-c.23G/c.23T heterozygotes vs. <em>TMPRSS2</em>-c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. <em>In silico</em> analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"225 ","pages":"Pages 89-98"},"PeriodicalIF":3.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960874","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
Glial overexpression of Tspo extends lifespan and protects against frataxin deficiency in Drosophila 神经胶质过表达Tspo可延长果蝇的寿命并防止其缺乏 frataxin。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-05-14 DOI: 10.1016/j.biochi.2024.05.003
{"title":"Glial overexpression of Tspo extends lifespan and protects against frataxin deficiency in Drosophila","authors":"","doi":"10.1016/j.biochi.2024.05.003","DOIUrl":"10.1016/j.biochi.2024.05.003","url":null,"abstract":"<div><p>The translocator protein TSPO is an evolutionary conserved mitochondrial protein overexpressed in various contexts of neurodegeneration. Friedreich Ataxia (FA) is a neurodegenerative disease due to GAA expansions in the <em>FXN</em> gene leading to decreased expression of frataxin, a mitochondrial protein involved in the biosynthesis of iron-sulfur clusters. We previously reported that <em>Tspo</em> was overexpressed in a Drosophila model of this disease generated by CRISPR/Cas9 insertion of approximately 200 GAA in the intron of <em>fh</em>, the fly frataxin gene. Here, we describe a new Drosophila model of FA with 42 GAA repeats, called fh-GAAs. The smaller expansion size allowed to obtain adults exhibiting hallmarks of the FA disease, including short lifespan, locomotory defects and hypersensitivity to oxidative stress. The reduced lifespan was fully rescued by ubiquitous expression of human <em>FXN</em>, confirming that both frataxins share conserved functions. We observed that <em>Tspo</em> was overexpressed in heads and decreased in intestines of these fh-GAAs flies. Then, we further overexpressed <em>Tspo</em> specifically in glial cells and observed improved survival. Finally, we investigated the effects of <em>Tspo</em> overexpression in healthy flies. Increased longevity was conferred by glial-specific overexpression, with opposite effects in neurons. Overall, this study highlights protective effects of glial TSPO in Drosophila both in a neurodegenerative and a healthy context.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"224 ","pages":"Pages 71-79"},"PeriodicalIF":3.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030090842400097X/pdfft?md5=906f7dad38442dc032f368a339c6c583&pid=1-s2.0-S030090842400097X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946212","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
FicD regulates adaptation to the unfolded protein response in the murine liver FicD调节小鼠肝脏对未折叠蛋白反应的适应。
IF 3.9 3区 生物学
Biochimie Pub Date : 2024-05-11 DOI: 10.1016/j.biochi.2024.05.012
Amanda K. Casey , Nathan M. Stewart , Naqi Zaidi , Hillery F. Gray , Amelia Cox , Hazel A. Fields , Kim Orth
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