{"title":"G-quadruplex in cancer energy metabolism: A potential therapeutic target","authors":"Zongqiang Han , Lina Wen","doi":"10.1016/j.bbagen.2025.130810","DOIUrl":"10.1016/j.bbagen.2025.130810","url":null,"abstract":"<div><div>In recent years, energy metabolism in cancer has received increasing attention as an important component of tumor biology, and the functions of transcription factors, mitochondria, reactive oxygen species (ROS) and the autophagy-lysosome system in which have been elucidated. G-quadruplex (G4) is a molecular switch that regulates gene transcription or translation. As an anticancer target, the effect of G4 on cancer cell proliferation, apoptosis, cycle and autophagy has been recognized. The energy metabolism system is a unified whole composed of transcription factors, metabolic regulators, metabolites and signaling pathways that run through the entire cancer process. However, the role of G4 in this complex metabolic network has not been systematically elucidated. In this review, we analyze the close correlation between G4 and transcription factors, mitochondria, ROS and the autophagy-lysosome system and suggest that G4 can exert a marked effect on cancer energy metabolism by regulating the above mentioned key regulatory elements. The anticancer effects of some G4 ligands through regulation of energy metabolism have also been summarized, confirming the clear involvement of G4 in energy metabolism. Although much more research is needed, we propose that G4 may play a critical role in the complex energy metabolism system of cancer, which is a promising target for anticancer strategies focusing on energy metabolism.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130810"},"PeriodicalIF":2.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870198","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}
{"title":"Pipecolic acid: A positive regulator of systemic acquired resistance and plant immunity","authors":"Megha Kumari , Prashansa Sharma , Archana Singh","doi":"10.1016/j.bbagen.2025.130808","DOIUrl":"10.1016/j.bbagen.2025.130808","url":null,"abstract":"<div><div>Pipecolic acid (Pip) is a naturally occurring non-protein amino acid, that builds up in plants in response to pathogen infection. Pip is upregulated in autophagy mutants, indicating its role as a crucial regulator of plant immunity by upregulating systemic acquired resistance (SAR). This broad-spectrum defense mechanism protects uninfected parts of the plant during subsequent pathogen attacks. Pip has been identified as a SAR chemical signal and acts before the NO-ROS-AzA-G3P. The biosynthesis of Pip begins with lysine by the activity of ALD1 and SARD4 in a sequential manner; ALD1, a lysine aminotransferase, catabolizes lysine to Δ 1-piperidine-2-carboxylic acid, which is further modified to Pip by the activity of ornithine cyclodeaminase activity of SARD4. Additionally, FMO 1, a flavin monooxygenase, catalyzes the synthesis of N-hydroxy-pipecolic acid (NHP, the final, SAR-inducing defense hormone) from Pip. Pip and its active form accumulate at the infection site in the phloem and are transported to distal parts of the plant via symplast to trigger SAR. This review focuses on the roles of Pip and NHP in regulating SAR and how they interact with other defense signals like salicylic acid (SA) to modulate plant immunity.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130808"},"PeriodicalIF":2.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878617","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}
Sho Oasa , Borislav Stoyanov , Yuta Hamada , Stanko N. Nikolić , Aleksandar J. Krmpot , Akira Kitamura , Vladana Vukojević
{"title":"Celebrating 50 years of fluorescence correlation spectroscopy (FCS): Advancing live-cell massively parallel FCS studies with photostable GFPs, mStayGold and StayGold/E138D","authors":"Sho Oasa , Borislav Stoyanov , Yuta Hamada , Stanko N. Nikolić , Aleksandar J. Krmpot , Akira Kitamura , Vladana Vukojević","doi":"10.1016/j.bbagen.2025.130809","DOIUrl":"10.1016/j.bbagen.2025.130809","url":null,"abstract":"<div><div>More than 50 years after its inception, fluorescence correlation spectroscopy (FCS) remains a cornerstone technique for quantitative characterization of the cellular dynamics of molecules and their concentration and interactions in live cells. The enhanced green fluorescent protein (eGFP) has long been a preferred tag in live-cell FCS, valued for its brightness, photostability and lack of posttranslational modifications. However, low eGFP photostability limits measurement durations, posing challenges for studying dynamic cellular processes necessitating longer measurement time. Recent advancements in fluorescent protein engineering have yielded mStayGold and StayGold/E138D, two highly photostable monomeric GFP variants. In this study, we evaluate their performance in live cells and utility for FCS by quantifying glucocorticoid receptor (GR) homodimerization and nuclear import/export dynamics in live cells. Our study shows that both mStayGold and StayGold/E138D exhibit twice the brightness of eGFP, significantly enhancing the signal-to-noise ratio (SNR). Using massively parallel FCS (mpFCS) and two-foci cross-correlation to characterize the direction of GR nucleocytoplasmic transport along the nuclear envelope, we also confirm that these proteins show significantly improved photostability over eGFP.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130809"},"PeriodicalIF":2.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870199","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}
Rahul Sahoo , Sriya Pattnaik , Biswajit Mohanty , Showkat Ahmad Mir , Birendra Behera
{"title":"Aryl hydrocarbon receptor (AHR) signalling: A double-edged sword guiding both cancer progression and cancer therapy","authors":"Rahul Sahoo , Sriya Pattnaik , Biswajit Mohanty , Showkat Ahmad Mir , Birendra Behera","doi":"10.1016/j.bbagen.2025.130805","DOIUrl":"10.1016/j.bbagen.2025.130805","url":null,"abstract":"<div><div>Aryl Hydrocarbon Receptor (AHR) reported to be associated with major carcinogenic signalling cascades which cause cell proliferations, metastasis and invasion as well as immune imbalance. AHR Participates in cellular processes not only through genomic pathways to cause genomic alterations but also via nongenomic pathways to alter various cytoplasmic proteins. In addition, AHR senses a wide range of ligands that modulate its downstream mechanisms that are intricated in cancer induction and prevention. Thus, AHR functions as a two-sided sword where some AHR ligands contribute to enhance cancer whereas few are useful for cancer treatment. Therefore, AHR represent as a regulatory point in cancer progression and treatment. There is a need to reinvestigate the regulatory role of AHR in major intracellular pathways and to explore the potential of AHR ligand for the design of cancer therapeutics. This review emphasizes the interaction of AHR with pro-carcinogenic signalling pathways that modulate cancer induction and progression. Furthermore, it also discusses about the current discovery of AHR ligands for cancer initiation or inhibition. This information could be useful for development of therapeutic strategies for the management of cancer by targeting AHR.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130805"},"PeriodicalIF":2.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830019","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}
{"title":"Harmonizing time with survival: Circadian rhythm and autophagy in plants","authors":"Laha Supriya , Deepika Dake , Mehanathan Muthamilarasan","doi":"10.1016/j.bbagen.2025.130807","DOIUrl":"10.1016/j.bbagen.2025.130807","url":null,"abstract":"<div><h3>Background</h3><div>Circadian rhythm (CR) is a self-sustaining biological oscillation that synchronizes physiological processes with the Earth's 24-h light-dark cycle. In plants, it regulates crucial physiological functions. Autophagy, a conserved degradation mechanism, maintains cellular homeostasis by recycling damaged organelles and proteins. Emerging evidence suggests an interplay between CRs and autophagy, optimizing plant survival and productivity.</div></div><div><h3>Scope</h3><div>This review explores the molecular mechanisms underlying CR and autophagy, highlighting their roles in growth and stress adaptation. It further examines how circadian clock components regulate autophagy-related genes (ATGs) in response to external cues.</div></div><div><h3>Major conclusions</h3><div>CR fine-tune autophagy by temporally regulating ATG gene expression. Key transcription factors, including TOC1 and LUX, modulate autophagic activity, ensuring energy conservation. Autophagy reciprocally influences circadian signaling, adjusting metabolic balance under stress.</div></div><div><h3>General significance</h3><div>Despite extensive research on circadian regulation, a comprehensive understanding of how core clock components orchestrate ATG gene expression remains lacking. Understanding the crosstalk between CR and autophagy provides insights into plant resilience and productivity, potentially informing crop improvement strategies that enhance stress tolerance and resource efficiency. This review aims to bridge this gap by summarizing recent insights and proposing future research directions.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130807"},"PeriodicalIF":2.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829960","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}
Michela Bruschi, Sofia Masini, Federica Biancucci, Giovanni Piersanti, Barbara Canonico, Michele Menotta, Mauro Magnani, Alessandra Fraternale
{"title":"Redox modulation via a synthetic thiol compound reshapes energy metabolism in endothelial cells and ameliorates angiogenic expression in a co-culture study with activated macrophages","authors":"Michela Bruschi, Sofia Masini, Federica Biancucci, Giovanni Piersanti, Barbara Canonico, Michele Menotta, Mauro Magnani, Alessandra Fraternale","doi":"10.1016/j.bbagen.2025.130803","DOIUrl":"10.1016/j.bbagen.2025.130803","url":null,"abstract":"<div><div>The vascular endothelium is the first interface exposed to circulating compounds and oxidative as well as pro-inflammatory <em>stimuli</em>. Nowadays, cysteine pro-drugs are emerging as new and potential therapies in cardiovascular and inflammatory diseases due to their cytoprotective effects. In this study, the effects of redox modulation by a synthetic thiol compound, i.e., I-152, a precursor of <em>N</em>-acetylcysteine (NAC) and cysteamine (MEA), were evaluated after 6 h and 24 h treatment on human umbilical cord endothelial cell (HUVECs) energy metabolism. Following I-152 treatment, higher cysteine and glutathione (GSH) content were detected via HPLC, in concomitance with I-152 derivatives, i.e., NAC and MEA. Untargeted metabolomics confirmed GSH upregulation and NAC presence in addition to I-152 itself and other metabolites, such as dithiol compound (NACMEAA) and triacetylated I-152. Mass spectrometry revealed that I-152 boosted ATP production, specifically through the mitochondrial OXPHOS, as determined via Seahorse assay without inducing oxidative stress. Additionally, I-152 treatment of HUVECs before co-culture with LPS-stimulated macrophages provided GSH and cysteine sustainment and attenuated the transcription of adhesion molecules as well as <em>iNOS</em> expression. Identifying the impact of redox regulation in physiological conditions and the possible metabolic targets could aid the application of novel thiol-based therapeutics.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130803"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786054","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}
Fuko Horie, Ryoko Ando, Koharu Sekimoto, Vo Thi Anh Nguyet, Shingo Izawa
{"title":"Yeast Hsp78 plays an essential role in adapting to severe ethanol stress via mild ethanol stress pretreatment in mitochondrial protein quality control","authors":"Fuko Horie, Ryoko Ando, Koharu Sekimoto, Vo Thi Anh Nguyet, Shingo Izawa","doi":"10.1016/j.bbagen.2025.130804","DOIUrl":"10.1016/j.bbagen.2025.130804","url":null,"abstract":"<div><div>Severe ethanol stress (10 % v/v) causes the denaturation and aggregation of certain mitochondrial proteins, such as aconitase (Aco1), forming the deposits of unfolded mitochondrial proteins (DUMPs) in the budding yeast <em>Saccharomyces cerevisiae</em>. Pre-exposing yeast cells to mild stress often induces adaptation to subsequent severe stress. However, whether pre-exposing yeast cells to mild ethanol stress mitigates mitochondrial protein aggregation remains unclear. Therefore, in this study, we examined the effects of pre-exposing yeast cells to mild ethanol stress on the yeast mitochondrial protein quality control (mtPQC) system under severe ethanol stress. Pretreatment with 6 % (v/v) ethanol significantly mitigated the formation of DUMPs and Aco1 aggregates under subsequent 10 % ethanol stress in wild-type cells but not in <em>hsp78</em>∆ and <em>mdj1</em>∆ cells. Pretreatment with 6 % ethanol increased the protein levels of mtPQC-related factors, Hsp78, Mdj1, and Hsp10; however, <em>hsp78</em>∆ cells showed significantly lower levels of Ssc1 (mtHsp70) and its co-chaperone Mdj1 than wild-type cells. Moreover, intracellular reactive oxygen species levels and the frequency of respiration-deficient mutants under 10 % ethanol stress were reduced after pretreatment with 6 % ethanol in wild-type cells but not in <em>hsp78</em>∆ cells. Overall, this study demonstrated that pre-exposing yeast cells to mild ethanol stress mitigated ethanol-induced mitochondrial damage by activating the mtPQC system, including <em>HSP78</em> expression, providing novel insights into the effects of ethanol stress on mitochondria and the corresponding responses in yeast.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130804"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787636","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}
Seung-Min Lee , Ju Yeon Kwak , Dongryeol Ryu , Yeo Jin Shin , Younglang Lee , Yong Ryoul Yang , Kwang-Pyo Lee , Jae Myoung Suh , Ki-Sun Kwon
{"title":"High glucose induces FABP3-mediated membrane rigidity via downregulation of SIRT1","authors":"Seung-Min Lee , Ju Yeon Kwak , Dongryeol Ryu , Yeo Jin Shin , Younglang Lee , Yong Ryoul Yang , Kwang-Pyo Lee , Jae Myoung Suh , Ki-Sun Kwon","doi":"10.1016/j.bbagen.2025.130802","DOIUrl":"10.1016/j.bbagen.2025.130802","url":null,"abstract":"<div><div>High glucose induces an atypical lipid composition in skeletal muscle, leading to loss of muscle mass and strength. However, the mechanisms underlying this glucose toxicity are not fully understood. Analysis of genes associated with a phenotype using the BXD phenome resource revealed that increased <em>Fabp3</em> expression in skeletal muscle correlated with hyperglycemia. FABP3 expression was also increased in hyperglycemic mouse models such as leptin-deficient <em>ob/ob</em>, <em>Ins2</em>Akita, and high-fat fed mice, as well as in aged mice. In cultured myotubes, high glucose elevated the mRNA and protein levels of FABP3, which contributes to decreased membrane fluidity, along with other mechanisms. FABP3 expression was dependent on the NAD<sup>+</sup>/NADH ratio and SIRT1 activity, suggesting a mechanism by which FABP3 is upregulated in hyperglycemic conditions. Our findings propose that FABP3 links hyperglycemia to atypical membrane physicochemical properties, which may weaken contractile and metabolic function, particularly in skeletal muscle.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130802"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759688","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}
{"title":"Inhibitors of inflammasome (NLRP3) signaling pathway as promising therapeutic candidates for oral cancer","authors":"Shreya Agrawal , Shatakshi Narang , Yadvendra Shahi , Sayali Mukherjee","doi":"10.1016/j.bbagen.2025.130800","DOIUrl":"10.1016/j.bbagen.2025.130800","url":null,"abstract":"<div><div>Inflammasomes are complex protein assemblies responsible for regulating the development and release of proinflammatory cytokines like interleukin-1beta (IL-1β) and interleukin-18 (IL-18) against the intracellular triggers. Among these, the Nod-like receptor protein 3 (NLRP3) inflammasome stands out as the most extensively studied and well-characterized member, implicated in numerous pathological conditions. A systematic literature search was conducted on the PubMed such as PubMed, Scopus, Google Scholar database to identify peer-reviewed publications pertaining to the role of NLRP3 in oral cancer pathogenesis and its inhibitors for targeted therapy. Recent research highlights the emerging significance of the NLRP3 inflammasome in tumorigenesis, garnering attention as a potential target for anticancer therapies. This review delves into the involvement of NLRP3 in cancer development and progression, providing an in-depth overview of its activation (and inhibition) and its impact on oral cancer pathogenesis. The manuscript provides a detailed review of the natural and synthetic compounds inhibiting the NLRP3 signaling pathway, which might act as therapeutic lead molecules in oral cancer. This holds promise to overcome targeted and effective treatment options the development of novel drugs targeting the NLRP3 inflammasome-mediated mechanisms in oral cancer.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130800"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769156","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}
Zhiliang Xiao , Yuan Wang , Dehua Pan , Xin Liu , Jin Gan , Liang Huang , Yan Feng
{"title":"USP3 promotes clear cell renal cell carcinoma progression by stabilizing MYC and enhancing glycolysis","authors":"Zhiliang Xiao , Yuan Wang , Dehua Pan , Xin Liu , Jin Gan , Liang Huang , Yan Feng","doi":"10.1016/j.bbagen.2025.130801","DOIUrl":"10.1016/j.bbagen.2025.130801","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal malignancy, and the deubiquitinase USP3 has been implicated as a critical factor in tumor biology. However, the precise mechanisms by which USP3 contributes to ccRCC progression remain unclear. This study investigates the role of USP3 in ccRCC and elucidates its underlying molecular mechanisms. Data from TCGA and GTEx databases showed elevated USP3 expression in ccRCC tissues and cell lines compared to normal renal tissues. Further analysis using qPCR and Western blot confirmed this upregulation in ccRCC cell lines. Functional assays revealed that silencing USP3 significantly impaired cell proliferation, migration, and invasion, while promoting apoptosis. Additionally, co-immunoprecipitation assays demonstrated an interaction between USP3 and MYC, with subsequent ubiquitination assays showing that USP3 regulates MYC stability. USP3 depletion also led to alterations in glycolysis-related gene expression, which could be partially reversed by MYC overexpression. These findings suggest that USP3 modulates ccRCC progression by stabilizing MYC, highlighting its potential as a therapeutic target in ccRCC treatment.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130801"},"PeriodicalIF":2.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747224","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}