Biochimie最新文献_第9页

The cellular SFPQ protein as a positive factor in the HIV-1 integration 细胞 SFPQ 蛋白是 HIV-1 整合的积极因素。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-17 DOI: 10.1016/j.biochi.2024.02.002

Тatiana Kikhai , Yulia Agapkina , Maria Silkina , Tatiana Prikazchikova , Marina Gottikh

{"title":"The cellular SFPQ protein as a positive factor in the HIV-1 integration","authors":"Тatiana Kikhai , Yulia Agapkina , Maria Silkina , Tatiana Prikazchikova , Marina Gottikh","doi":"10.1016/j.biochi.2024.02.002","DOIUrl":"10.1016/j.biochi.2024.02.002","url":null,"abstract":"<div>The cellular SFPQ protein is involved in several stages of the HIV-1 life cycle, but the detailed mechanism of its involvement is not yet fully understood. Here, the role of SFPQ in the early stages of HIV-1 replication has been studied. It is found that changes in the intracellular level of SFPQ affect the integration of viral DNA, but not reverse transcription, and SFPQ is a positive factor of integration. A study of the SFPQ interaction with HIV-1 integrase (IN) has revealed two diRGGX1-4 motifs in the N-terminal region of SFPQ, which are involved in IN binding. Substitution of a single amino acid residue in any of these regions led to a decrease in binding efficiency, while mutations in both motifs almost completely disrupted the SFPQ interaction with IN. The effect of the SFPQ mutants with impaired ability to bind IN on viral replication has been analyzed. Unlike the wild-type protein, the SFPQ mutants did not affect viral integration. This confirms that SFPQ influences the integration stage through direct interaction with IN. Our results indicate that the SFPQ/IN complex can be considered as a potential therapeutic target for the development of new inhibitors of HIV replication.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 9-17"},"PeriodicalIF":3.9,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907129","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

Renal ischemia and reperfusion impact the purinergic signaling in a vascular bed distant from the injured site 肾脏缺血和再灌注会影响远离受伤部位的血管床的嘌呤能信号传导。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-13 DOI: 10.1016/j.biochi.2024.02.003

Jeferson Stabile , Raquel Silva Neres-Santos , Isabela Dorta Molina Hernandes , Carolina Victória Cruz Junho , Geovane Felippe Alves , Isabella Cardoso Silva , Marcela Sorelli Carneiro-Ramos , Cristina Ribas Fürstenau

{"title":"Renal ischemia and reperfusion impact the purinergic signaling in a vascular bed distant from the injured site","authors":"Jeferson Stabile , Raquel Silva Neres-Santos , Isabela Dorta Molina Hernandes , Carolina Victória Cruz Junho , Geovane Felippe Alves , Isabella Cardoso Silva , Marcela Sorelli Carneiro-Ramos , Cristina Ribas Fürstenau","doi":"10.1016/j.biochi.2024.02.003","DOIUrl":"10.1016/j.biochi.2024.02.003","url":null,"abstract":"<div><h3>Aims</h3>Acute kidney injury (AKI) is a public health problem and represents a risk factor for cardiovascular diseases (CVD) and vascular damage. This study aimed to investigate the impact of AKI on purinergic components in mice aorta. Main methods: The kidney ischemia was achieved by the occlusion of the left kidney pedicle for 60 min, followed by reperfusion for 8 (IR8) and 15 (IR15) days. Renal function was assessed through biochemical assays, while gene expression levels were evaluated by RT-qPCR. Key findings: Analyses of renal parameters showed renal remodeling through mass loss in the left kidney and hypertrophy of the right kidney in the IR15 group. Furthermore, after 15 days, local inflammation was evidenced in the aorta. Moreover, the aorta purinergic components were significantly impacted by the renal ischemia and reperfusion model, with increases in gene expression of the pro-inflammatory purinoceptors P2Y1, P2Y2, P2Y6, and P2X4, potentially contributing to the vessel inflammation. The expression of NTPDase2 and ecto-5′-nucleotidase were also significantly increased in the aorta of the same group. In addition, both ATP and AMP hydrolysis were significantly increased in the aorta from IR15 animals, driving the entire purinergic cascade to the production of the anti-inflammatory adenosine. Significance: In short, this is the first time that inflammation of the aorta due to AKI was shown to have an impact on purinergic signaling components, with emphasis on the adenosinergic pathway. This seems to be closely implicated in the establishment of vascular inflammation in this model of AKI and deserves to be further investigated.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 37-44"},"PeriodicalIF":3.9,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000397/pdfft?md5=baca31c66f4512ff8951bd7eaf65f05e&pid=1-s2.0-S0300908424000397-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742943","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

Dynamics and metabolic effects of intestinal gases in healthy humans 健康人肠道气体的动力学和代谢效应

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-05 DOI: 10.1016/j.biochi.2024.02.001

Arturo Tozzi , Raffaele Minella

引用次数: 0

Multi-oligomeric and catalytically compromised serine acetyltransferase and cysteine regulatory complex of Mycobacterium tuberculosis 结核分枝杆菌的多异构体和催化功能受损的丝氨酸乙酰转移酶与半胱氨酸调节复合物

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-03 DOI: 10.1016/j.biochi.2024.01.009

Rahisuddin R , Payal Thakur , Narender Kumar, Neha Saini, Shrijta Banerjee, Ravi Pratap Singh, Madhuri Patel, S. Kumaran

{"title":"Multi-oligomeric and catalytically compromised serine acetyltransferase and cysteine regulatory complex of Mycobacterium tuberculosis","authors":"Rahisuddin R , Payal Thakur , Narender Kumar, Neha Saini, Shrijta Banerjee, Ravi Pratap Singh, Madhuri Patel, S. Kumaran","doi":"10.1016/j.biochi.2024.01.009","DOIUrl":"10.1016/j.biochi.2024.01.009","url":null,"abstract":"<div>l-cysteine, a primary building block of mycothiol, plays an essential role in the defense mechanism of Mycobacterium tuberculosis (Mtb). However, it is unclear how Mtb regulates cysteine biosynthesis as no study has reported the cysteine regulatory complex (CRC) in Mtb. Serine acetyltransferase (SAT) and cysteine synthase (CS) interact to form CRC. Although MtCS has been characterized well, minimal information is available on MtSAT, which synthesizes, O-acetylserine (OAS), the precursor of cysteine. This study fills the gap and provides experimental evidence for the presence of MtCRC and a non-canonical multi-oligomeric MtSAT. We employed multiple analytical methods to characterize the oligomeric and kinetic properties of MtSAT and MtCRC. Results show that MtSAT, lacking >75 N-terminal amino acids exists in three different assembly states; trimer, hexamer, and dodecamer, compared to the single hexameric state of SAT of other bacteria. While hexamers display the highest catalytic turnover, the trimer is the least active. The predominance of trimers at low physiologically relevant concentrations suggests that MtSAT displays the lowest catalytic potential known. Further, the catalytic potential of MtSAT is also significantly reduced in CRC state, in contrast to enhanced activity of SAT in CRC of other organisms. Our study provides insights into multi-oligomeric MtSAT with reduced catalytic potential and demonstrates that both MtSAT and MtCS of Mycobacterium interact to form CRC, although with altered catalytic properties. We discuss our results in light of the altered biochemistry of the last step of canonical sulfate-dependent cysteine biosynthesis of Mycobacterium.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":"Pages 110-124"},"PeriodicalIF":3.9,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669626","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

Role of the Escherichia coli FocA and FocB formate channels in controlling proton/potassium fluxes and hydrogen production during osmotic stress in energy-limited, stationary phase fermenting cells 大肠杆菌 FocA 和 FocB 甲酸盐通道在能量受限的静止期发酵细胞渗透压胁迫期间控制质子/钾通量和氢气产生的作用

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-01 DOI: 10.1016/j.biochi.2024.01.017

A. Babayan , A. Vassilian , A. Poladyan , K. Trchounian

{"title":"Role of the Escherichia coli FocA and FocB formate channels in controlling proton/potassium fluxes and hydrogen production during osmotic stress in energy-limited, stationary phase fermenting cells","authors":"A. Babayan , A. Vassilian , A. Poladyan , K. Trchounian","doi":"10.1016/j.biochi.2024.01.017","DOIUrl":"10.1016/j.biochi.2024.01.017","url":null,"abstract":"<div>Escherichia coli FocA and FocB formate channels export formate or import it for further disproportionation by the formate hydrogenlyase (FHL) complex to H2 and CO2. Here, we show that under pH and osmotic stress FocA and FocB play important roles in regulating proton and potassium fluxes and couple this with H2 production in stationary-phase cells. Using whole-cell assays with glucose as electron donor, a focB mutant showed a 50 % decrease in VH2, while N’N’-dicyclohexylcarbodiimide (DCCD) treatment of osmotically stressed cells underlined the role of FOF1 ATPase in H2 production. At pH 7.5 and under osmotic stress FocB contributed to the proton flux but not to the potassium flux. At pH 5.5 both formate channels contributed to the proton and potassium fluxes. Particulalry, a focA mutant had 40 % lower potassium flux whereas the proton flux increased approximately two-fold. Moreover, at pH 5.5H2 production was totally inhibited by DCCD in the focA mutant. Taken together, our results suggest that depending on external pH, the formate channels play an important role in osmoregulation by helping to balance proton/potassium fluxes and H2 production, and thus assist the proton FOF1-ATPase in maintenance of ion gradients in fermenting stationary-phase cells.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":"Pages 91-98"},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669255","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

Cell cycle and mitosis progression during ZIKA virus infection: The viral non-structural protein NS5 as a master regulator of the APC/cyclosome? ZIKA病毒感染过程中的细胞周期和有丝分裂进程：病毒非结构蛋白 NS5 是 APC/细胞周期体的主调控因子？

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-01 DOI: 10.1016/j.biochi.2024.01.016

Grégorie Lebeau , Mathilde Hoareau , Sébastien Rivière , Daed El Safadi , Christine Robert Da Silva , Pascale Krejbich-Trotot , Wildriss Viranaicken

{"title":"Cell cycle and mitosis progression during ZIKA virus infection: The viral non-structural protein NS5 as a master regulator of the APC/cyclosome?","authors":"Grégorie Lebeau , Mathilde Hoareau , Sébastien Rivière , Daed El Safadi , Christine Robert Da Silva , Pascale Krejbich-Trotot , Wildriss Viranaicken","doi":"10.1016/j.biochi.2024.01.016","DOIUrl":"10.1016/j.biochi.2024.01.016","url":null,"abstract":"<div>Alterations in cell cycle regulation contribute to Zika virus (ZIKV)-associated pathogenesis and may have implications for the development of therapeutic avenues. As a matter of fact, ZIKV alters cell cycle progression at multiple stages, including G1, S, G2, and M phases. During a cell cycle, the progression of mitosis is particularly controlled to avoid any abnormalities in cell division. In this regard, the critical metaphase-anaphase transition is triggered by the activation of anaphase-promoting complex/cyclosome (APC/C) by its E3 ubiquitin ligase subunit Cdc20. Cdc20 recognizes substrates by interacting with a destruction box motif (D-box). Recently, the ZIKV nonstructural protein 5 (NS5), one of the most highly conserved flavivirus proteins, has been shown to localize to the centrosome in each pole and to spindle fibers during mitosis. Inducible expression of NS5 reveals an interaction of this viral factor with centrosomal proteins leading to an increase in the time required to complete mitosis. By analyzing the NS5 sequence, we discovered the presence of a D-box. Taken together, these data support the idea that, in addition to its role in viral replication, NS5 plays a critical role in the control of the cell cycle of infected cells and, more specifically, in the regulation of the mitotic spindle. Here we propose that the NS5 protein may interfere with the metaphase-anaphase progression, and thus cause the observed delay in mitosis via the regulation of APC/C.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":"Pages 75-80"},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669422","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

Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation 是否应该重新考虑细胞能量代谢的标准模式？磷酸戊糖途径、糖酵解和线粒体外氧化磷酸化之间可能存在的耦合关系

IF 3.9 3区生物学

Biochimie Pub Date : 2024-02-01 DOI: 10.1016/j.biochi.2024.01.018

Alessandro Maria Morelli , Felix Scholkmann

{"title":"Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation","authors":"Alessandro Maria Morelli , Felix Scholkmann","doi":"10.1016/j.biochi.2024.01.018","DOIUrl":"10.1016/j.biochi.2024.01.018","url":null,"abstract":"<div>The process of cellular respiration occurs for energy production through catabolic reactions, generally with glucose as the first process step. In the present work, we introduce a novel concept for understanding this process, based on our conclusion that glucose metabolism is coupled to the pentose phosphate pathway (PPP) and extra-mitochondrial oxidative phosphorylation in a closed-loop process. According to the current standard model of glycolysis, glucose is first converted to glucose 6-phosphate (glucose 6-P) and then to fructose 6-phosphate, glyceraldehyde 3-phosphate and pyruvate, which then enters the Krebs cycle in the mitochondria. However, it is more likely that the pyruvate will be converted to lactate. In the PPP, glucose 6-P is branched off from glycolysis and used to produce NADPH and ribulose 5-phosphate (ribulose 5-P). Ribulose 5-P can be converted to fructose 6-P and glyceraldehyde 3-P. In our view, a circular process can take place in which the ribulose 5-P produced by the PPP enters the glycolysis pathway and is then retrogradely converted to glucose 6-P. This process is repeated several times until the complete degradation of glucose 6-P. The role of mitochondria in this process is to degrade lipids by beta-oxidation and produce acetyl-CoA; the function of producing ATP appears to be only secondary. This proposed new concept of cellular bioenergetics allows the resolution of some previously unresolved controversies related to cellular respiration and provides a deeper understanding of metabolic processes in the cell, including new insights into the Warburg effect.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":"Pages 99-109"},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000361/pdfft?md5=c3fd924a6d74efb403fc49f2ab3630c6&pid=1-s2.0-S0300908424000361-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669595","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

Isoprenylcysteine carboxyl methyltransferase (ICMT) promotes invadopodia formation and metastasis in cancer cells 异戊烯基半胱氨酸羧基甲基转移酶（ICMT）可促进癌细胞中侵袭性细胞嵴的形成和转移

IF 3.9 3区生物学

Biochimie Pub Date : 2024-01-30 DOI: 10.1016/j.biochi.2024.01.015

Carla Borini Etichetti , Evelyn Arel Zalazar , Carolina Di Benedetto , Nabila Cocordano , Sabrina Valente , Silvio Bicciato , Mauricio Menacho-Márquez , María Cecilia Larocca , Javier Girardini

{"title":"Isoprenylcysteine carboxyl methyltransferase (ICMT) promotes invadopodia formation and metastasis in cancer cells","authors":"Carla Borini Etichetti , Evelyn Arel Zalazar , Carolina Di Benedetto , Nabila Cocordano , Sabrina Valente , Silvio Bicciato , Mauricio Menacho-Márquez , María Cecilia Larocca , Javier Girardini","doi":"10.1016/j.biochi.2024.01.015","DOIUrl":"10.1016/j.biochi.2024.01.015","url":null,"abstract":"<div>Isoprenyl cysteine carboxyl methyltransferase (ICMT) catalyzes the last step of the prenylation pathway. Previously, we found that high ICMT levels enhance tumorigenesis in vivo and that its expression is repressed by the p53 tumor suppressor. Based on evidence suggesting that some ICMT substrates affect invasive traits, we wondered if this enzyme may promote metastasis. In this work, we found that ICMT overexpression enhanced lung metastasis in vivo. Accordingly, ICMT overexpression also promoted cellular functions associated with aggressive phenotypes such as migration and invasion in vitro. Considering that some ICMT substrates are involved in the regulation of actin cytoskeleton, we hypothesized that actin-rich structures, associated with invasion and metastasis, may be affected. Our findings revealed that ICMT enhanced the formation of invadopodia. Additionally, by analyzing cancer patient databases, we found that ICMT is overexpressed in several tumor types. Furthermore, the concurrent expression of ICMT and CTTN, which encodes a crucial component of invadopodia, showed a significant correlation with clinical outcome. In summary, our work identifies ICMT overexpression as a relevant alteration in human cancer that promotes the development of metastatic tumors.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 28-36"},"PeriodicalIF":3.9,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139648757","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

Identification and characterisation of a novel interaction between oestrogen receptor alpha and FOXP2 雌激素受体 alpha 和 FOXP2 之间新型相互作用的鉴定和特征描述

IF 3.9 3区生物学

Biochimie Pub Date : 2024-01-29 DOI: 10.1016/j.biochi.2024.01.014

Aasiya Lakhi, Sylvia Fanucchi

{"title":"Identification and characterisation of a novel interaction between oestrogen receptor alpha and FOXP2","authors":"Aasiya Lakhi, Sylvia Fanucchi","doi":"10.1016/j.biochi.2024.01.014","DOIUrl":"10.1016/j.biochi.2024.01.014","url":null,"abstract":"<div>Forkhead box P2 (FOXP2) regulates expression of various genes and is associated with language, speech and neural development as well as cancer. Since there may be a putative link between sex and language and because transcription factors rarely function in isolation, this study aims to investigate whether FOXP2 directly associates with oestrogen receptor α (ER1), a nuclear receptor responsible for sexual differentiation that is also associated with cancer. Isothermal titration calorimetry and fluorescence anisotropy were used to investigate the interaction between the DNA-binding forkhead domain (FHD) of FOXP2, the N-terminal region (NT) of FOXP2, and the ligand-binding domain (LBD) of ER1. ER1 LBD does not interact with FOXP2 NT but associates with apo-FOXP2 FHD in an enthalpically favourable manner. The affinity of this interaction is inversely correlated to the salt concentration. Additionally, FOXP2 FHD that is bound to ER1 LBD, has reduced ability to interact with its cognate DNA. This research identifies a novel interaction between ER1 LBD and FOXP2 FHD and shows that the interaction is regulated by salt. Moreover, FOXP2 FHD cannot bind to both ER1 LBD and DNA simultaneously, suggesting that this interaction could be involved in regulating the transcriptional pathway of FOXP2 should the interaction be found in vivo. This study could serve as a foundation for uncovering the basis of sexual dimorphism in speech and language development and related disorders and potentially offers an alternate for targeted cancer therapies.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139578266","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

Translocator protein (TSPO) ligands attenuate mitophagy deficits in the SH-SY5Y cellular model of Alzheimer's disease via the autophagy adaptor P62 转运蛋白（TSPO）配体通过自噬适配体 P62 减轻阿尔茨海默病 SH-SY5Y 细胞模型中的有丝分裂缺陷。

IF 3.3 3区生物学

Biochimie Pub Date : 2024-01-26 DOI: 10.1016/j.biochi.2024.01.012

{"title":"Translocator protein (TSPO) ligands attenuate mitophagy deficits in the SH-SY5Y cellular model of Alzheimer's disease via the autophagy adaptor P62","authors":"","doi":"10.1016/j.biochi.2024.01.012","DOIUrl":"10.1016/j.biochi.2024.01.012","url":null,"abstract":"<div>Mitochondrial dysfunction has been widely implicated in the pathogenesis of Alzheimer's disease (AD), with accumulation of damaged and dysfunctional mitochondria occurring early in the disease. Mitophagy, which governs mitochondrial turnover and quality control, is impaired in the AD brain, and strategies aimed at enhancing mitophagy have been identified as promising therapeutic targets. The translocator protein (TSPO) is an outer mitochondrial membrane protein that is upregulated in AD, and ligands targeting TSPO have been shown to exert neuroprotective effects in mouse models of AD. However, whether TSPO ligands modulate mitophagy in AD has not been explored. Here, we provide evidence that the TSPO-specific ligands Ro5-4864 and XBD173 attenuate mitophagy deficits and mitochondrial fragmentation in a cellular model of AD overexpressing the human amyloid precursor protein (APP). Ro5-4864 and XBD173 appear to enhance mitophagy via modulation of the autophagic cargo receptor P62/SQSTM1, in the absence of an effect on PARK2, PINK1, or LC3 level. Taken together, these findings indicate that TSPO ligands may be promising therapeutic agents for ameliorating mitophagy deficits in AD.</div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"224 ","pages":"Pages 132-138"},"PeriodicalIF":3.3,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000300/pdfft?md5=4162ccdd08d1fbf1250a9d43647aaac5&pid=1-s2.0-S0300908424000300-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572381","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