International Journal of Biochemistry & Cell Biology最新文献

{"title":"Transcriptomic and in silico analysis of BLACE (B-cell acute lymphoblastic leukemia expressed), a new non-coding RNA, as a diagnostic biomarker in B-cell ALL","authors":"Saadiya Zia ,&nbsp;Nazia Rehman ,&nbsp;Saima Ejaz ,&nbsp;Muhammad Shahid ,&nbsp;Muhammad Ali ,&nbsp;Ramla Shahid","doi":"10.1016/j.biocel.2024.106698","DOIUrl":"10.1016/j.biocel.2024.106698","url":null,"abstract":"<div><div>ALL (acute lymphoblastic leukemia) is a type of hematological malignancy that involves developmental and differentiation arrest at the lymphoblast stage. BLACE, a gene specifically expressed in B-cell acute lymphoblastic leukemia shows little or no expression in mature B-lymphocytes. The current pilot study involves transcriptional analysis of BLACE in B-cell ALL patients. Expression of BLACE was high in both pediatric and adult ALL patients. Promoter analysis of the BLACE gene showed the presence of CAAT and TATA box promoters and G-rich sequences with a potential to form G-quadruplexes. Due to identification of TAL1 transcription factor binding sites within the BLACE promoter region, expression of TAL1 gene was measured and found to correlate with the BLACE expression. The presence of an overlapping G-rich sequence and TAL1 binding site at −1291 bps within BLACE promoter indicated a new target site for controlling BLACE expression. The docking studies performed between BLACE-TAL1 protein showed a binding score of −208.68 kcal/mol and identified 21 BLACE nucleotide - TAL1 residues interacting at the docking interface. Together, our findings suggested that BLACE gene specifically expressed in B-cell ALL could serve as a new therapeutic target. Further investigations are required to get a comprehensive understanding of the BLACE gene mechanism.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106698"},"PeriodicalIF":3.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689402","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":"MLN4924 Suppresses head and neck squamous cell carcinoma progression by inactivating the mTOR signaling pathway via the NEDD8/CUL4/TSC2 axis","authors":"Youfang Jiang ,&nbsp;Fei Le ,&nbsp;Shuangling Huang ,&nbsp;Xuezhong Chen ,&nbsp;Ziqing Deng","doi":"10.1016/j.biocel.2024.106696","DOIUrl":"10.1016/j.biocel.2024.106696","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a five-year survival rate below 50 %. Standard treatments for HNSCC include surgery, radiotherapy, chemotherapy, and targeted therapies, but they still have significant limitations. Neddylation, a post-translational modification involving the attachment of NEDD8 (neural precursor cells expressed developmentally down-regulated 8) to proteins, is frequently dysregulated in HNSCC, thereby promoting tumor growth. MLN4924, also known as Pevonedistat, is a Neddylation inhibitor that has shown promise in suppressing HNSCC cell proliferation and invasion, establishing it as a potential therapeutic option. However, its precise molecular mechanism remains unclear. This study aims to investigate the mechanism of MLN4924 in HNSCC. This study examined the effects of MLN4924 on HNSCC and its associated molecular pathways. Bioinformatic analysis indicated that NEDD8, a critical component of the Neddylation pathway, is linked to poor prognosis and the mTOR (mammalian target of rapamycin) signaling pathway in HNSCC. MLN4924 significantly suppressed cell migration, invasion, and the epithelial-mesenchymal transition (EMT) pathway, and downregulated NEDD8 expression. Mechanistic studies demonstrated that MLN4924 inhibited the binding of NEDD8 to cullin4 (CUL4) and prevented the Neddylation of tuberous sclerosis complex 2 (TSC2), leading to the inactivation of the mTOR pathway. These findings were confirmed <em>in vivo</em>, where MLN4924 effectively inhibited tumor growth. Overall, MLN4924 disrupted Neddylation pathway and stabilized TSC2, thereby inactivating the mTOR pathway. The study provided a theoretical basis for the clinical potential of MLN4924 in improving treatment outcomes for HNSCC patients, offering a novel strategy for addressing this challenging disease.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106696"},"PeriodicalIF":3.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683280","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}

{"title":"Human pluripotent stem cell-derived models of the hippocampus","authors":"Haruka Nishimura ,&nbsp;Yun Li","doi":"10.1016/j.biocel.2024.106695","DOIUrl":"10.1016/j.biocel.2024.106695","url":null,"abstract":"<div><div>The hippocampus is a crucial structure of the brain, recognised for its roles in the formation of memory, and our ability to navigate the world. Despite its importance, clear understanding of how the human hippocampus develops and its contribution to disease is limited due to the inaccessible nature of the human brain. In this regard, the advent of human pluripotent stem cell (hPSC) technologies has enabled the study of human biology in an unprecedented manner, through the ability to model development and disease as both 2D monolayers and 3D organoids. In this review, we explore the existing efforts to derive the hippocampal lineage from hPSCs and evaluate the various aspects of the <em>in vivo</em> hippocampus that are replicated <em>in vitro.</em> In addition, we highlight key diseases that have been modelled using hPSC-derived cultures and offer our perspective on future directions for this emerging field.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106695"},"PeriodicalIF":3.4,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669573","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}

{"title":"Prolonged glutamine starvation reactivates mTOR to inhibit autophagy and initiate autophagic lysosome reformation to maintain cell viability","authors":"Amruta Singh ,&nbsp;Kewal Kumar Mahapatra ,&nbsp;Prakash Priyadarshi Praharaj ,&nbsp;Srimanta Patra ,&nbsp;Soumya Ranjan Mishra ,&nbsp;Sankargouda Patil ,&nbsp;Sujit Kumar Bhutia","doi":"10.1016/j.biocel.2024.106694","DOIUrl":"10.1016/j.biocel.2024.106694","url":null,"abstract":"<div><div>Autophagy, a cellular recycling mechanism, utilizes lysosomes for cellular degradation. Prolonged autophagy reduces the pool of functional lysosomes in the cell. However, lysosomal homeostasis is maintained through the regeneration of functional lysosomes during the terminal stage of autophagy, i.e. Autophagic lysosome reformation (ALR). Through confocal microscopy during glutamine starvation, we unravel the regeneration of tubules from autolysosomes by undertaking significant membrane remodeling, which majorly depends on mTOR reactivation, RAB7 dissociation, phosphatidyl inositol 3 phosphate (PI3P) dependent-dynamin 2 and clathrin recruitment. In glutamine-starved cells, we found mTOR is the central modulator in regulating ALR initiation, and its pharmacological inhibition with rapamycin leads to a decrease in lysosomal tubulation. Moreover, RAB7 and Clathrin are essential for tubule elongation and it showed that siRNA targeting RAB7 and Clathrin restricts tubule initiation under glutamine starvation. In this setting, we examined the physiological relevance of ALR during prolonged glutamine deprivation and found that genetic and pharmacological inhibition of critical proteins involved in ALR promotes cell death in oral cancer cells, establishing ALR is essential for maintaining cell survival during stress.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106694"},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640192","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":"Regulation of autophagy by Rab27B in colorectal cancer","authors":"Sahida Afroz ,&nbsp;Ranjan Preet ,&nbsp;Vikalp Vishwakarma ,&nbsp;Andrew E. Evans ,&nbsp;Alexa N. Magstadt ,&nbsp;Dan A. Dixon","doi":"10.1016/j.biocel.2024.106693","DOIUrl":"10.1016/j.biocel.2024.106693","url":null,"abstract":"<div><div>Autophagy is a cellular recycling process that is associated with tumor growth, anti-tumor immune responses, and therapy resistance in colorectal cancer (CRC). In this report, we identify the small GTPase Rab27B to control the autophagy process in CRC. Depletion of Rab27B showed an abnormal accumulation of autophagy vesicles and increased autophagy markers in CRC cells, indicating autophagy dysregulation. Image analysis indicated that autophagy flux is blocked at the autophagosome/lysosome fusion step when Rab27B is lost. While Rab27B deficient cells are proficient at growth under 2D <em>in vitro</em> conditions, cell growth was significantly impacted in both <em>in vitro</em> 3D growth and <em>in vivo</em> tumorigenesis studies. Together, these results demonstrate a new role of Rab27B in the autophagy trafficking process in CRC and identify Rab27B as a potential therapeutic target for CRC.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106693"},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631038","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}

{"title":"TFAP2C/FLT3 axis reduces ferroptosis in breast cancer cells by inhibiting mitochondrial autophagy","authors":"Jiayue Shen ,&nbsp;Yali He ,&nbsp;Bingchuan Zhou ,&nbsp;Huabo Qin ,&nbsp;Shuai Zhang ,&nbsp;Zixiang Huang ,&nbsp;Xiangcheng Zhang","doi":"10.1016/j.biocel.2024.106691","DOIUrl":"10.1016/j.biocel.2024.106691","url":null,"abstract":"<div><h3>Background</h3><div>FMS-like tyrosine kinase 3 (FLT3), a key target protein for treating acute myeloid leukemia, has recently been found to be closely related to ferroptosis in breast cancer (BC). However, the mechanism by which FLT3 regulates ferroptosis in BC remains unknown. Whether this regulatory relationship can be exploited for BC treatment needs further exploration.</div></div><div><h3>Methods</h3><div>This study combined analysis from The Cancer Genome Atlas database with immunohistochemistry/quantitative reverse transcription-PCR/Western blot experiments to verify the expression of FLT3 in BC. FLT3 knockdown/overexpression plasmids were used in conjunction with mitochondrial autophagy inducers to treat BC cells, analyzing the effects of FLT3 on autophagy and ferroptosis. Key transcription factors for FLT3 were determined through predictions from the KnockTF database and dual luciferase/chromatin immunoprecipitation experiments, further analyzing the impact of this regulatory axis on autophagy and ferroptosis in BC cells.</div></div><div><h3>Results</h3><div>FLT3 was significantly overexpressed in BC tissues and cells. Overexpression of FLT3 could inhibit autophagy and ferroptosis in BC cells, a regulation that was restored upon the addition of mitochondrial autophagy inducers. Additionally, transcription factor AP-2 gamma (TFAP2C) could mediate the transcriptional activation of FLT3, further inhibiting ferroptosis induced by mitochondrial autophagy.</div></div><div><h3>Conclusion</h3><div>The TFAP2C/FLT3 axis reduced ferroptosis in BC cells by inhibiting mitochondrial autophagy. These research findings elucidated the mechanism by which FLT3 regulated ferroptosis in BC and provided potential targets for BC treatment.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106691"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631041","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":"Long non-coding RNA AC105118.1 affects glycolysis to facilitate oxaliplatin resistance in colorectal cancer cells by modulating the miR-378a-3p/KIF26B axis","authors":"Yong Zhang,&nbsp;Zhiling Shen,&nbsp;Xiaodong Han,&nbsp;Yachao Wu,&nbsp;Tianchen Huang","doi":"10.1016/j.biocel.2024.106692","DOIUrl":"10.1016/j.biocel.2024.106692","url":null,"abstract":"<div><h3>Background</h3><div>Oxaliplatin is a first-line chemotherapy drug for colorectal cancer (CRC), but many patients eventually lose treatment efficacy due to acquired resistance. AC105118.1 is a long non-coding RNA with unknown biological function. This research attempts to probe into the molecular regulatory mechanism of AC105118.1 in CRC oxaliplatin resistance.</div></div><div><h3>Methods</h3><div>The expression level of AC105118.1 in CRC tissues and cells was measured based on The Cancer Genome Atlas (TCGA) data and quantitative reverse transcription polymerase chain reaction (qRT-PCR). We utilized dual-luciferase assay and RNA immunoprecipitation to analyze the interaction between AC105118.1, miR-378a-3p, and their downstream target KIF26B. CCK-8, colony formation assay, and flow cytometry were employed to assess the half inhibitory concentration (IC₅₀), cell proliferation, and apoptosis rate of HCT116/L-OHP cells treated with oxaliplatin. The glycolysis evaluation was completed by measuring the extracellular acidification rate (ECAR), glucose consumption, lactate production, and glycolysis-related proteins (HK2, GLUT1, and LDHA). TUNEL staining was used to detect the level of apoptosis.</div></div><div><h3>Results</h3><div>AC105118.1 was specifically upregulated in CRC tissues and cells. AC105118.1 indirectly facilitated the expression of miRNA target gene KIF26B by sequestering miR-378a-3p. In HCT116/L-OHP cells, transfection with si-AC105118.1 resulted in a decrease in glycolysis level, a lower maximum IC₅₀ required for oxaliplatin-treated cells, inhibited cell proliferation, and an increase in apoptosis rate. All of these effects were alleviated when simultaneously transfecting miR-378a-3p inhibitor or oe-KIF26B. Knockdown of AC105118.1 significantly inhibited oxaliplatin resistance to CRC in mice.</div></div><div><h3>Conclusion</h3><div>AC105118.1 facilitates glycolysis and increases CRC cells’ resistance to oxaliplatin by targeting the miR-378a-3p/KIF26B axis. The present work shed new insights into the function and mechanism of AC105118.1 in molecular function and suggested that the AC105118.1/miR-378a-3p/KIF26B axis is a promising target for intervening CRC oxaliplatin resistance.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106692"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630904","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":"Myc functions downstream of InR and their concurrent upregulation additively restricts pathogenesis of human poly(Q) disorders in Drosophila disease models","authors":"Shweta Tandon ,&nbsp;Surajit Sarkar","doi":"10.1016/j.biocel.2024.106690","DOIUrl":"10.1016/j.biocel.2024.106690","url":null,"abstract":"<div><div>Human polyglutamine [poly(Q)] disorders are caused by abnormal expansion of CAG repeats in one gene (disease specific), yet a plethora of cellular pathways are found to be involved in their pathogenesis and progression. Despite the tremendous effort, all pursuits for the development of intervention therapy against these disorders seem futile. Recent reports suggest combination therapy as a potential strategy to combat the complex pathogenesis of such neurodegenerative disorders. The present study attempted to identify a combinatorial intervention strategy against human poly(Q) disorders in <em>Drosophila</em> disease models. Due to its immense potential to be stimulated by drugs, the evolutionarily conserved insulin signalling cascade which is well-established modifier of human poly(Q) pathogenesis was selected for the study. Genetic screening studies identified <em>Drosophila</em> Myc as a potential partner of insulin receptor (InR) that conferred additive rescue against poly(Q) induced neurodegeneration. Comprehensive analyses demonstrated InR and Myc to confer additive rescue against several events of pathogenesis, including aggregation of expanded poly(Q) containing proteins, transcriptional dysregulation, upsurge of cell death cascades, etc. Also, the synergistic rescue efficiency of InR and Myc was equally efficient in mitigating poly(Q) induced structural and functional deficits. The study also demonstrates that Myc functions downstream of InR signalling cascade to deliver rescue against human poly(Q) mediated toxicity in <em>Drosophila</em> disease models. In conclusion, the present study suggests that InR and Myc have the potential to be developed as a combinatorial therapeutic approach against human poly(Q) diseases.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106690"},"PeriodicalIF":3.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630995","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":"Integrative multi-omics and big data analysis of global nutrition and radiotherapy trends","authors":"Sibo Meng ,&nbsp;Dizhi Jiang ,&nbsp;Guanghui Yang ,&nbsp;Kaiyue Guo ,&nbsp;Enhao Yu ,&nbsp;Yun Wang ,&nbsp;Linli Qu ,&nbsp;Jiaxin Li","doi":"10.1016/j.biocel.2024.106687","DOIUrl":"10.1016/j.biocel.2024.106687","url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy serves as a crucial modality in cancer treatment, frequently synergizing with other therapies to enhance patient outcomes. Unfortunately, radiotherapy is often accompanied by nutritional impairments, including dysphagia and malnutrition, which hinder patient recovery and treatment efficacy. Moreover, nutritional abnormalities accompanied by metabolic reprogramming may lead to alterations across multiple omics domains. Consequently, big data analysis on radiotherapy and nutrition is imperative.</div></div><div><h3>Objective</h3><div>This study employs bibliometric analysis to visually showcase the current research landscape and trending hotspots in the intersection of nutrition and radiotherapy.</div></div><div><h3>Methods</h3><div>Leveraging the Web of Science Core Collection, we screened and analyzed 4379 publications related to nutrition and radiotherapy published between 2004 and 2023. Utilizing VOSviewer, Bibliometrix, and Citespace software, we conducted bibliometric analysis and visualization of countries, institutions, authors, and keywords.</div></div><div><h3>Results</h3><div>Our analysis reveals a substantial increase in publications concerning nutrition and radiotherapy, with the United States and China leading in both publication volume and citation impact. The research focus has gradually shifted from phenomenological studies to mechanistic investigations, as evidenced by changes in keyword usage. While confirming the influence of nutritional status on radiotherapy outcomes, we also identified potential links to genomics, proteomics, metabolomics, and other omics disciplines.</div></div><div><h3>Conclusion</h3><div>This study emphasizes the growing attention to the interplay between nutrition and radiotherapy in cancer treatment. Our findings suggest that further integration of multi-omics analysis can enhance understanding of the mechanisms underlying these interactions, providing a foundation for advancing cancer diagnosis and treatment strategies in the future.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106687"},"PeriodicalIF":3.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631222","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":"Mitochondrial E3 ligase TRIM71 affects mitochondrial complex assembly and sensitizes dopaminergic neuronal cells to apoptosis in Parkinson’s Disease (PD)","authors":"Shanikumar Goyani,&nbsp;Shatakshi Shukla,&nbsp;Minal Mane,&nbsp;M.V. Saranga,&nbsp;Nisha Chandak,&nbsp;Anjali Shinde,&nbsp;Fatema Currim,&nbsp;Jyoti Singh,&nbsp;Rajesh Singh","doi":"10.1016/j.biocel.2024.106689","DOIUrl":"10.1016/j.biocel.2024.106689","url":null,"abstract":"<div><div>Parkinson’s Disease (PD) is a chronic neurodegenerative disorder that impacts the substantia niagra region of the midbrain leading to impaired motor as well as non-motor symptoms of the central nervous system (CNS). Mitochondrial dysfunction has been characterized as the primary cause of dopaminergic neuronal loss, however, the molecular mechanisms leading to mitochondrial dysfunction are not completely understood. PARKIN, E3 ubiquitin ligase, plays a crucial role in maintaining mitochondrial quality control, albeit the role of other E3 ligases in regulating mitochondrial functions is not understood. In the current study, we explored the implication of TRIM71, E3 ubiquitin ligase, in the modulation of mitochondrial functions and neuronal death in PD stress conditions induced by rotenone and 6-OHDA. Ectopic expression of TRIM71 in SH-SY5Y dopaminergic neuronal cells sensitizes to PD stress-induced cell death, while its knock-down rescues neuronal cell death. TRIM71 turnover is enhanced in neurons under PD stress conditions. TRIM71 predominantly localizes on the outer mitochondrial membrane and translocation increases during PD stress conditions. TRIM71 regulates mitochondrial complex I and IV assembly and activity. TRIM71 knock-down decreases mitochondrial ROS and enhances ATP level as well as mitochondrial membrane potential in PD stress conditions. TRIM71-mediated mitochondrial ROS and cell death were rescued by mitoTEMPO, a mitochondrial-targeted antioxidant. Altogether, the evidence strongly suggests TRIM71-mediated modulation of mitochondrial functions and neuronal apoptosis in PD stress conditions.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"177 ","pages":"Article 106689"},"PeriodicalIF":3.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630907","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}