Pub Date : 2024-11-15DOI: 10.1016/j.cstres.2024.11.003
Paolo De Los Rios , Mathieu E. Rebeaud , Pierre Goloubinoff
{"title":"An outmoded in vitro-inferred mechanism for chaperonin-accelerated protein refolding is confirmed in cells by cryo-electron tomography","authors":"Paolo De Los Rios , Mathieu E. Rebeaud , Pierre Goloubinoff","doi":"10.1016/j.cstres.2024.11.003","DOIUrl":"10.1016/j.cstres.2024.11.003","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 764-768"},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643744","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}
Pub Date : 2024-11-06DOI: 10.1016/j.cstres.2024.11.001
Renzhong Li , Kui Sun
Osteoarthritis (OA), a common degenerative joint disease, is characterized by the apoptosis of chondrocytes as a primary pathophysiological change, with endoplasmic reticulum stress (ERS) playing a crucial role. It has been demonstrated that an imbalance in endoplasmic reticulum (ER) homeostasis can lead to ERS, activating three cellular adaptive response pathways through the unfolded protein response to restore ER homeostasis. Mild ERS exerts a protective effect on cells, while prolonged ERS that disrupts the self-regulatory balance of the ER activates apoptotic signaling pathways, leading to chondrocyte apoptosis and hastening OA progression. Hence, controlling the ERS signaling pathway and its apoptotic factors has become a critical focus for preventing and treating OA. This review aims to elucidate the key mechanisms of ERS pathway-induced apoptosis, associated targets, and regulatory pathways, offering valuable insights to enhance the mechanistic understanding of OA. It also reviews the mechanisms studied for ERS-related drugs or compounds for the treatment of OA.
骨关节炎（OA）是一种常见的关节退行性疾病，以软骨细胞凋亡为主要病理生理变化，其中内质网应激（ERS）起着至关重要的作用。研究表明，内质网（ER）平衡失调可导致ERS，通过未折叠蛋白反应（UPR）激活三种细胞适应性反应途径，以恢复ER平衡。轻度的ERS对细胞有保护作用，而长时间的ERS会破坏内质网的自我调节平衡，激活细胞凋亡信号通路，导致软骨细胞凋亡，加速OA进展。因此，控制 ERS 信号通路及其凋亡因子已成为预防和治疗 OA 的关键重点。本综述旨在阐明ERS通路诱导凋亡的关键机制、相关靶点和调控途径，为加深对OA的机理认识提供有价值的见解。本综述还回顾了用于治疗 OA 的 ERS 相关药物或化合物的研究机制。
{"title":"Regulation of chondrocyte apoptosis in osteoarthritis by endoplasmic reticulum stress","authors":"Renzhong Li , Kui Sun","doi":"10.1016/j.cstres.2024.11.001","DOIUrl":"10.1016/j.cstres.2024.11.001","url":null,"abstract":"<div><div>Osteoarthritis (OA), a common degenerative joint disease, is characterized by the apoptosis of chondrocytes as a primary pathophysiological change, with endoplasmic reticulum stress (ERS) playing a crucial role. It has been demonstrated that an imbalance in endoplasmic reticulum (ER) homeostasis can lead to ERS, activating three cellular adaptive response pathways through the unfolded protein response to restore ER homeostasis. Mild ERS exerts a protective effect on cells, while prolonged ERS that disrupts the self-regulatory balance of the ER activates apoptotic signaling pathways, leading to chondrocyte apoptosis and hastening OA progression. Hence, controlling the ERS signaling pathway and its apoptotic factors has become a critical focus for preventing and treating OA. This review aims to elucidate the key mechanisms of ERS pathway-induced apoptosis, associated targets, and regulatory pathways, offering valuable insights to enhance the mechanistic understanding of OA. It also reviews the mechanisms studied for ERS-related drugs or compounds for the treatment of OA.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 750-763"},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615217","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}
Pub Date : 2024-10-24DOI: 10.1016/j.cstres.2024.10.005
Yanzhao Li , Jing Yan , Pingzhen Yang
{"title":"Corrigendum to “The mechanism and therapeutic strategies in doxorubicin induced cardiotoxicity: Role of programmed cell death” [Cell Stress Chaperones. 2024;29:666-680]","authors":"Yanzhao Li , Jing Yan , Pingzhen Yang","doi":"10.1016/j.cstres.2024.10.005","DOIUrl":"10.1016/j.cstres.2024.10.005","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Page 720"},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495873","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}
Pub Date : 2024-10-23DOI: 10.1016/j.cstres.2024.10.006
Milad J. Alasady , Marc L. Mendillo
The heat shock factor (HSF) family of transcription factors drives gene expression programs that maintain cytosolic protein homeostasis (proteostasis) in response to a vast array of physiological and exogenous stressors. The importance of HSF function has been demonstrated in numerous physiological and pathological contexts. Evidence accumulating over the last two decades has revealed that the regulatory programs driven by the HSF family can vary dramatically depending on the context in which it is activated. To broadly maintain proteostasis across these contexts, HSFs must bind and appropriately regulate the correct target genes at the correct time. Here, we discuss “the heat shock factor code”—our current understanding of how human cells use HSF paralog diversification and interplay, local concentration, post-translational modifications, and interactions with other proteins to enable the functional plasticity required for cellular resilience across a multitude of environments.
{"title":"The heat shock factor code: Specifying a diversity of transcriptional regulatory programs broadly promoting stress resilience","authors":"Milad J. Alasady , Marc L. Mendillo","doi":"10.1016/j.cstres.2024.10.006","DOIUrl":"10.1016/j.cstres.2024.10.006","url":null,"abstract":"<div><div>The heat shock factor (HSF) family of transcription factors drives gene expression programs that maintain cytosolic protein homeostasis (proteostasis) in response to a vast array of physiological and exogenous stressors. The importance of HSF function has been demonstrated in numerous physiological and pathological contexts. Evidence accumulating over the last two decades has revealed that the regulatory programs driven by the HSF family can vary dramatically depending on the context in which it is activated. To broadly maintain proteostasis across these contexts, HSFs must bind and appropriately regulate the correct target genes at the correct time. Here, we discuss “the heat shock factor code”—our current understanding of how human cells use HSF paralog diversification and interplay, local concentration, post-translational modifications, and interactions with other proteins to enable the functional plasticity required for cellular resilience across a multitude of environments.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 735-749"},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495872","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}
Pub Date : 2024-10-18DOI: 10.1016/j.cstres.2024.10.004
Brenda A. Schilke , Thomas Ziegelhoffer , Przemyslaw Domanski , Jaroslaw Marszalek , Bartlomiej Tomiczek , Elizabeth A. Craig
Protein factors bind ribosomes near the tunnel exit, facilitating protein trafficking and folding. In eukaryotes, the heterodimeric nascent polypeptide-associated complex (NAC) is the most abundant—equimolar to ribosomes. Saccharomyces cerevisiae has a minor β-type subunit (Nacβ2) in addition to abundant Nacβ1, and therefore two NAC heterodimers, α/β1 and α/β12. The additional beta NAC gene arose at the time of the whole genome duplication that occurred in the S. cerevisiae lineage. Nacβ2 has been implicated in regulating the fate of messenger RNA encoding ribosomal protein Rpl4 during translation via its interaction with the Caf130 subunit of the regulatory CCR4-Not complex. We found that Nacβ2 residues just C-terminal to the globular domain are required for its interaction with Caf130 and its negative effect on the growth of cells lacking Acl4, the specialized chaperone for Rpl4. Substitution of these Nacβ2 residues at homologous positions in Nacβ1 results in a chimeric protein that interacts with Caf130 and slows the growth of ∆acl4 cells lacking Nacβ2. Furthermore, alteration of residues in the N-terminus of Nacβ2 or chimeric Nacβ1 previously shown to affect ribosome binding overcomes the growth defect of ∆acl4. Our results are consistent with a model in which Nacβ2’s ribosome association per se or its precise positioning is necessary for productive recruitment of CCR4-Not via its interaction with the Caf130 subunit to drive Rpl4 messenger RNA degradation.
{"title":"Functional similarities and differences among subunits of the nascent polypeptide-associated complex (NAC) of Saccharomyces cerevisiae","authors":"Brenda A. Schilke , Thomas Ziegelhoffer , Przemyslaw Domanski , Jaroslaw Marszalek , Bartlomiej Tomiczek , Elizabeth A. Craig","doi":"10.1016/j.cstres.2024.10.004","DOIUrl":"10.1016/j.cstres.2024.10.004","url":null,"abstract":"<div><div>Protein factors bind ribosomes near the tunnel exit, facilitating protein trafficking and folding. In eukaryotes, the heterodimeric nascent polypeptide-associated complex (NAC) is the most abundant—equimolar to ribosomes. <em>Saccharomyces cerevisiae</em> has a minor β-type subunit (Nacβ2) in addition to abundant Nacβ1, and therefore two NAC heterodimers, α/β1 and α/β12. The additional beta NAC gene arose at the time of the whole genome duplication that occurred in the <em>S. cerevisiae</em> lineage. Nacβ2 has been implicated in regulating the fate of messenger RNA encoding ribosomal protein Rpl4 during translation <em>via</em> its interaction with the Caf130 subunit of the regulatory CCR4-Not complex. We found that Nacβ2 residues just C-terminal to the globular domain are required for its interaction with Caf130 and its negative effect on the growth of cells lacking Acl4, the specialized chaperone for Rpl4. Substitution of these Nacβ2 residues at homologous positions in Nacβ1 results in a chimeric protein that interacts with Caf130 and slows the growth of ∆<em>acl4</em> cells lacking Nacβ2. Furthermore, alteration of residues in the N-terminus of Nacβ2 or chimeric Nacβ1 previously shown to affect ribosome binding overcomes the growth defect of ∆<em>acl4</em>. Our results are consistent with a model in which Nacβ2’s ribosome association <em>per se</em> or its precise positioning is necessary for productive recruitment of CCR4-Not <em>via</em> its interaction with the Caf130 subunit to drive Rpl4 messenger RNA degradation.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 721-734"},"PeriodicalIF":3.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459007","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}
Pub Date : 2024-10-11DOI: 10.1016/j.cstres.2024.10.003
Lawrence E. Hightower
{"title":"In memoriam James S. Clegg (1933–2024)","authors":"Lawrence E. Hightower","doi":"10.1016/j.cstres.2024.10.003","DOIUrl":"10.1016/j.cstres.2024.10.003","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 718-719"},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459008","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}
Pub Date : 2024-10-10DOI: 10.1016/j.cstres.2024.10.002
Rebecca A. Sager , Sarah J. Backe , Jennifer Heritz , Mark R. Woodford , Dimitra Bourboulia , Mehdi Mollapour
The serine/threonine Protein Phosphatase-5 (PP5) plays an essential role in regulating hormone and stress-induced signaling networks as well as extrinsic apoptotic pathways in cells. Unlike other Protein Phosphatases, PP5 possesses both regulatory and catalytic domains, and its function is further modulated through post-translational modifications (PTMs). PP5 contains a tetratricopeptide repeat (TPR) domain, which usually inhibits its phosphatase activity by blocking the active site (closed conformation). Certain activators bind to the PP5–TPR domain, alleviating this inhibition and allowing the catalytic domain to adopt an active (open) conformation. While this mechanism has been proposed based on structural and biophysical studies, PP5 conformational changes and activity have yet to be observed in cells. Here, we designed and developed a flow cytometry-based fluorescence resonance energy transfer (FC-FRET) method, enabling real-time observation of PP5 autoinhibition and activation within live mammalian cells. By quantifying FRET efficiency using sensitized emission, we established a standardized and adaptable data acquisition workflow. Our findings revealed that, in a cellular context, PP5 exists in multiple conformational states, none of which alone fully predicts its activity. Additionally, we have demonstrated that PTMs such as phosphorylation and SUMOylation impact PP5 conformational changes, representing a significant advancement in our understanding of its regulatory mechanisms.
{"title":"Flow cytometry FRET reveals post-translational modifications drive Protein Phosphatase-5 conformational changes in mammalian cells","authors":"Rebecca A. Sager , Sarah J. Backe , Jennifer Heritz , Mark R. Woodford , Dimitra Bourboulia , Mehdi Mollapour","doi":"10.1016/j.cstres.2024.10.002","DOIUrl":"10.1016/j.cstres.2024.10.002","url":null,"abstract":"<div><div>The serine/threonine Protein Phosphatase-5 (PP5) plays an essential role in regulating hormone and stress-induced signaling networks as well as extrinsic apoptotic pathways in cells. Unlike other Protein Phosphatases, PP5 possesses both regulatory and catalytic domains, and its function is further modulated through post-translational modifications (PTMs). PP5 contains a tetratricopeptide repeat (TPR) domain, which usually inhibits its phosphatase activity by blocking the active site (closed conformation). Certain activators bind to the PP5–TPR domain, alleviating this inhibition and allowing the catalytic domain to adopt an active (open) conformation. While this mechanism has been proposed based on structural and biophysical studies, PP5 conformational changes and activity have yet to be observed in cells. Here, we designed and developed a flow cytometry-based fluorescence resonance energy transfer (FC-FRET) method, enabling real-time observation of PP5 autoinhibition and activation within live mammalian cells. By quantifying FRET efficiency using sensitized emission, we established a standardized and adaptable data acquisition workflow. Our findings revealed that, in a cellular context, PP5 exists in multiple conformational states, none of which alone fully predicts its activity. Additionally, we have demonstrated that PTMs such as phosphorylation and SUMOylation impact PP5 conformational changes, representing a significant advancement in our understanding of its regulatory mechanisms.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 709-717"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459006","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}
Pub Date : 2024-10-04DOI: 10.1016/j.cstres.2024.10.001
Chuanlan Liu , Xiaomu Zhu , Erbu Aga , Wai Ming Tse , Kathy Wai Gaun Tse , Yanyong Liu , Bengui Ye
Ebeiedinone and peimisine are the major active ingredients of Fritillariae Cirrhosae Bulbus. In this study, we looked at how these two forms of isosteroidal alkaloids protect human bronchial epithelial BEAS-2B cells from oxidative stress and apoptosis caused by cigarette smoke extract (CSE). First, the cytotoxicity was determined using the CCK8 assay, and an oxidative stress model was established. Then the antioxidative stress activity and mechanism were investigated by ELISA, flow cytometry, and Western blotting. By the CCK-8 assay, exposure to CSE (20%, 40%, and 100%) reduced the viability of BEAB-2S cells. The flow cytometry findings indicated that CSE-induced production of ROS (0.5% to maximum) and treatments with 10 μM ebeiedinone and 20 μM peimisine attenuated the production of ROS. The western blot assay results indicate that ebeiedinone and peimisine reduce CSE-induced oxidative stress, DNA damage, apoptosis, and autophagy dysregulation by inhibiting ROS, upregulating SOD and GSH/GSSG, and downregulating MDA, 4-HNE, and 8-OHdG through the NRF2/KEAP1 and JNK/MAPK-dependent pathways, thereby delaying the pathological progression of COPD caused by CS.Our data suggest that CSE causes oxidative stress, DNA damage, and apoptosis in BEAS-2B cells, as well as the progression of COPD. Ebeiedinone and peimisine fight CS-induced COPD by suppressing autophagy deregulation and apoptosis.
{"title":"Ebeiedinone and peimisine inhibit cigarette smoke extract-induced oxidative stress injury and apoptosis in BEAS-2B cells","authors":"Chuanlan Liu , Xiaomu Zhu , Erbu Aga , Wai Ming Tse , Kathy Wai Gaun Tse , Yanyong Liu , Bengui Ye","doi":"10.1016/j.cstres.2024.10.001","DOIUrl":"10.1016/j.cstres.2024.10.001","url":null,"abstract":"<div><div>Ebeiedinone and peimisine are the major active ingredients of Fritillariae Cirrhosae Bulbus. In this study, we looked at how these two forms of isosteroidal alkaloids protect human bronchial epithelial BEAS-2B cells from oxidative stress and apoptosis caused by cigarette smoke extract (CSE). First, the cytotoxicity was determined using the CCK8 assay, and an oxidative stress model was established. Then the antioxidative stress activity and mechanism were investigated by ELISA, flow cytometry, and Western blotting. By the CCK-8 assay, exposure to CSE (20%, 40%, and 100%) reduced the viability of BEAB-2S cells. The flow cytometry findings indicated that CSE-induced production of ROS (0.5% to maximum) and treatments with 10 μM ebeiedinone and 20 μM peimisine attenuated the production of ROS. The western blot assay results indicate that ebeiedinone and peimisine reduce CSE-induced oxidative stress, DNA damage, apoptosis, and autophagy dysregulation by inhibiting ROS, upregulating SOD and GSH/GSSG, and downregulating MDA, 4-HNE, and 8-OHdG through the NRF2/KEAP1 and JNK/MAPK-dependent pathways, thereby delaying the pathological progression of COPD caused by CS.Our data suggest that CSE causes oxidative stress, DNA damage, and apoptosis in BEAS-2B cells, as well as the progression of COPD. Ebeiedinone and peimisine fight CS-induced COPD by suppressing autophagy deregulation and apoptosis.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"29 6","pages":"Pages 697-708"},"PeriodicalIF":3.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380110","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}
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