Philosophical transactions of the Royal Society of London. Series B, Biological sciences最新文献_第3页

HSP60 and HSP10 depletion provoke distinct biological responses. HSP60和HSP10的损耗引起不同的生物学反应。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2026.0194

Hila Ben-David, Shani Gabbay, Sufa Sued-Hendrickson, Linor Cohen, Liron Levin, Nili Tickotsky Moskovitz, Ifat Abramovich, Shiran Dror, Yariv Brotman, Shai Kaluski-Kopach, Evelina Nikelshparg, Anat Ben-Zvi, Barak Rotblat

{"title":"HSP60 and HSP10 depletion provoke distinct biological responses.","authors":"Hila Ben-David, Shani Gabbay, Sufa Sued-Hendrickson, Linor Cohen, Liron Levin, Nili Tickotsky Moskovitz, Ifat Abramovich, Shiran Dror, Yariv Brotman, Shai Kaluski-Kopach, Evelina Nikelshparg, Anat Ben-Zvi, Barak Rotblat","doi":"10.1098/rstb.2026.0194","DOIUrl":"https://doi.org/10.1098/rstb.2026.0194","url":null,"abstract":"The mitochondrial chaperone and co-chaperone HSP60/HSP10 (HSPD1/ HSPE1), the mammalian homologues of bacterial GroEL/GroES, form a barrel-and-lid complex to fold newly imported or misfolded mitochondrial proteins. Several lines of evidence suggest that HSPD1 and HSPE1 have diverged in function. HSPD1 and HSPE1 are found in different clusters in the ecological network of gene expression in cancer. MTHFD2 was demonstrated to be an endogenous client protein of HSPD1 that does not require HSPE1 for its folding. Newly imported proteins show differential dependencies on HSP60 and HSP10 in isolated yeast mitochondria. Finally, HSPE1 was found to regulate a mitochondrial GTPase and modulate amyloid fibril formation independently of HSPD1. Nevertheless, the extent to which HSPD1 and HSPE1 have diverged in function has not been explored. Here, we show divergent transcriptomic and metabolic responses to the depletion of HSP60 versus HSP10 in cancer cells, and divergent activation of the mitochondrial unfolded protein response across tissues in Caenorhabditis elegans. Importantly, responses to HSP10 depletion were not nested within those of HSP60 depletion. We speculate that HSPE1 has diverged from HSPD1 and may have additional new cellular functions. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential proteostasis imbalance and the molecular basis of distinct synucleinopathies and tauopathies. 不同蛋白平衡失衡及不同突触核蛋白病和tau病的分子基础。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0272

Virginie Redeker, Ronald Melki

引用次数: 0

Adaptation to heat stress by diversification of the vertebrate heat shock transcription factor family. 脊椎动物热休克转录因子家族的多样化对热应激的适应。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0274

Ryosuke Takii, Mitsuaki Fujimoto, Akira Nakai

{"title":"Adaptation to heat stress by diversification of the vertebrate heat shock transcription factor family.","authors":"Ryosuke Takii, Mitsuaki Fujimoto, Akira Nakai","doi":"10.1098/rstb.2025.0274","DOIUrl":"https://doi.org/10.1098/rstb.2025.0274","url":null,"abstract":"Cells survive and reproduce by coping with acute or chronic exposure to a fixed elevated temperature or fluctuating temperatures. These properties are one of the main evolutionary forces and involve the heat shock response. This response is characterized by the induction of heat-shock proteins (HSPs) and is mainly regulated by heat-shock transcription factors (HSFs) in vertebrates. A single HSF is present in yeast and invertebrates, such as Caenorhabditis elegans and Drosophila, whereas vertebrates have evolved multiple HSFs. The potential of HSFs to induce HSP expression is linked to the amino acid conservation of their domains and regions that are responsible for transcriptional activation and appears to be associated with the homeothermic capacity of vertebrate animals in a thermally fluctuating environment. HSFs protect cells and organisms from heat stress by regulating not only their expression of HSPs that assist in protein folding and suppress protein misfolding and aggregation, but also the expression of genes related to protein clearance, metabolism, the cell cycle, DNA damage response, apoptosis, senescence, the cytoskeleton, extracellular matrix and inflammation. The diversification of HSF genes may expand the cellular capacity to adapt to thermal changes in vertebrate animals. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microplastics negatively impact ecosystems, human health and cellular proteostasis. 微塑料对生态系统、人类健康和细胞蛋白质平衡产生负面影响。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0268

Elise Kikis

{"title":"Microplastics negatively impact ecosystems, human health and cellular proteostasis.","authors":"Elise Kikis","doi":"10.1098/rstb.2025.0268","DOIUrl":"https://doi.org/10.1098/rstb.2025.0268","url":null,"abstract":"With the widespread use of plastics for both personal and industrial applications, significant amounts of micro- and nano-sized plastic particles (MNPs) are entering our air and waterways. This impacts ecosystems, triggers the formation of biofilms and facilitates the emergence of antibiotic-resistant bacteria. Moreover, direct human exposure to MNPS is inevitable and occurs primarily through ingestion and inhalation. Once internalized, MNPs cause oxidative stress and inflammation. Within tissue matrices, proteins and other macromolecules adhere to MNPs, forming a coating referred to as a corona. This corona provides the MNPs with biological identity that increases their propensity to enter cells and breach the blood-brain barrier. From a proteostasis perspective, proteins that physically interact with MNPs undergo conformational changes that result in the formation of a rigid β-sheet structure. This leads to amyloidogenesis in a manner that may pose a risk for neurodegenerative disease. This review synthesizes what is known about the properties of microplastics (MPs), their ecological impacts and their impacts on human health-with an emphasis on the ways that MP may interfere with the ability of cells and organisms to maintain healthy proteostasis. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The mitochondrial chaperone HSPD1 folds MTHFD2 independently of its co-chaperone HSPE1. 线粒体伴侣HSPD1独立于其共同伴侣HSPE1折叠MTHFD2。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0500

Shani Gabbay, Hila Ben-David, Shatha S Alassam, Linor Cohen, Tal Levy, Albert Batushansky, Shiran Dror, Moshe Elkabets, Noga Alon, Shai Kaluski-Kopach, Shimon Bershtein, Anat Ben-Zvi, Barak Rotblat

{"title":"The mitochondrial chaperone HSPD1 folds MTHFD2 independently of its co-chaperone HSPE1.","authors":"Shani Gabbay, Hila Ben-David, Shatha S Alassam, Linor Cohen, Tal Levy, Albert Batushansky, Shiran Dror, Moshe Elkabets, Noga Alon, Shai Kaluski-Kopach, Shimon Bershtein, Anat Ben-Zvi, Barak Rotblat","doi":"10.1098/rstb.2025.0500","DOIUrl":"https://doi.org/10.1098/rstb.2025.0500","url":null,"abstract":"Acquiring new cellular states entails metabolic reprogramming driven by changes in the expression of cytosolic and mitochondrial metabolic enzymes. Most mitochondrial proteins are synthesized in the cytosol and imported into the mitochondria in a linear form, after which they are folded by a network of mitochondrial chaperones and co-chaperones. Which mitochondrial protein is dependent upon which chaperone for its folding is largely unknown. HSPD1/HSPE1 (HSP60/HSP10) are evolutionarily conserved mammalian homologues of the bacterial proteins GroEL/GroES, forming a chamber-and-lid chaperonin to facilitate the folding of client proteins. The endogenous clients of HSP60 in mammalian cells are not fully known, nor are the HSP60 clients that require HSP10 for folding. We used gene knockdown and stable isotope labelling of amino acids in cell culture (SILAC)-based proteomics to identify HSPD1 client proteins. We found that HSPD1 supports the expression of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a key mitochondrial one-carbon (1C) pathway enzyme, in cells and tumours. In addition, HSPD1 directly folds MTHFD2 independently of its co-chaperone HSPE1. HSPD1 interacts with MTHFD2 in mitochondria, and MTHFD2 is degraded by LONP1 in HSPD1 knockdown cells. Our data show that HSPD1 is an MTHFD2 chaperone and can fold an endogenous client protein independently of HSPE1, providing a link between mitochondrial protein folding and the 1C pathway. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caenorhabditis elegans small heat-shock protein HSP-12.6 has a highly specialized protective function towards muscle thick filaments in vivo. 秀丽隐杆线虫小热休克蛋白HSP-12.6在体内对肌肉粗丝具有高度特化的保护功能。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0362

Abigail Fern, Jasmine Alexander-Floyd, Anhelina Volchok, Susan M Cahill, Srikar Donepudi, Jana Smuts, Tali Gidalevitz

{"title":"Caenorhabditis elegans small heat-shock protein HSP-12.6 has a highly specialized protective function towards muscle thick filaments in vivo.","authors":"Abigail Fern, Jasmine Alexander-Floyd, Anhelina Volchok, Susan M Cahill, Srikar Donepudi, Jana Smuts, Tali Gidalevitz","doi":"10.1098/rstb.2025.0362","DOIUrl":"https://doi.org/10.1098/rstb.2025.0362","url":null,"abstract":"Small heat-shock proteins (sHSPs) are an ancient and diverse class of molecular chaperones, acting as a first line of defence against proteotoxic stresses. While the canonical sHSPs prevent uncontrollable aggregation of a broad range of non-native substrates, a subset of sHSPs do not exhibit this broad activity in vitro, and their functions in vivo are poorly understood. Interestingly, several such sHSPs are selectively expressed in muscle tissues, including by myogenic programmes, indicating probable functional roles. We examined in vivo function of Caenorhabditis elegans HSP-12.6, which possesses no chaperone activity in vitro but regulates lifespan, and is developmentally induced in the muscles of long-lived dauer animals. We found that HSP-12.6 exhibits exceptional selectivity in protecting the muscle function against folding or assembly mutations in thick filament proteins, but not in thin filament or non-filament proteins. This selectivity paralleled its exclusive chaperone-like binding to either the healthy myosin-containing thick filaments or their aggregates. HSP-12.6 did not bind other muscle structures or aggregates, including those of thin filaments, and retained its selectivity when challenged with a toxic aggregation-prone polyQ protein. Our data establish that HSP-12.6 has a highly selective myoprotective activity, with a client spectrum distinct from other sHSPs. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of cellular proteostasis via mitochondrial protein import. 通过线粒体蛋白质输入调节细胞蛋白质稳态。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0271

Ngoc G T Nguyen, Jian Li

引用次数: 0

Cell-type-specific proteostasis networks differ across developing human organs. 细胞类型特异性的蛋白质静止网络在发育中的人体器官中是不同的。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0277

Johnny Cruz-Corchado, Veena Prahlad

{"title":"Cell-type-specific proteostasis networks differ across developing human organs.","authors":"Johnny Cruz-Corchado, Veena Prahlad","doi":"10.1098/rstb.2025.0277","DOIUrl":"https://doi.org/10.1098/rstb.2025.0277","url":null,"abstract":"Tremendous progress has been made in understanding how proteostasis networks (PNs)-chaperones, co-chaperones, the degradation machinery and associated factors-are regulated cell-autonomously to safeguard cell-type-specific proteomes. However, the extent to which the principles derived from single-cell studies operate within developing tissues, where organ-level cues and multicellular organization shape cellular behaviour, remains unresolved. To address this, we analysed the regulation of PN gene expression during human prenatal development by generating PN-centric maps from single-cell RNA-sequencing datasets of developing limb, skin and skeletal tissues from the Human Cell Atlas. Across tissues, PN expression generally aligned with the functional demands placed on major cell populations. However, transcriptionally similar cell types displayed distinct PN profiles depending on their organ context, indicating that PN composition is not solely dictated by cell identity. Moreover, we uncovered a hierarchy of regulatory control governing PN deployment. In the developing limb-where morphogenetic gradients strongly shape developmental trajectories-PN expression tracked developmental stage rather than differentiation state. By contrast, during skin and skeletal development, PN expression more closely reflected cell-type-specific functional programmes. Together, these findings reinforce the model that the PN is a dynamically deployed system governed by layered regulatory logic, rather than a fixed attribute of cell identity. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteostasis (in)action: the role of co-pathologies in neurodegenerative disease. 蛋白酶的作用：在神经退行性疾病中的共同病理的作用。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0273

James F Morley

{"title":"Proteostasis (in)action: the role of co-pathologies in neurodegenerative disease.","authors":"James F Morley","doi":"10.1098/rstb.2025.0273","DOIUrl":"https://doi.org/10.1098/rstb.2025.0273","url":null,"abstract":"Clinically distinct neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), share in common progressive neuronal dysfunction and cell death associated with the accumulation of misfolded proteins. Central to these processes are the cellular and organismal proteostasis networks responsible for maintaining protein homeostasis through coordinated actions of molecular chaperones, the ubiquitin-proteasome system and autophagy-lysosomal pathways. As a consequence of ageing, genetic modifications and other disease-specific conditions, the proteostatic network becomes compromised, leading to the accumulation of toxic protein aggregates that disrupt neuronal function and lead to neurodegeneration. Specific misfolded proteins are associated with each neurodegenerative disease (i.e. α-synuclein in PD, amyloid-β/tau in AD and TAR DNA-binding protein 43/SOD in ALS). However, increasing evidence implicates more complex interactions of co-pathologies across these disorders, as Lewy bodies are common in AD brains and Alzheimer pathology is present in the majority of PD autopsy cases. These observations are consistent with the idea that disruption of proteostasis networks by one aggregation-prone protein could result in misfolding and aggregation of other neurodegeneration-related species. This review will examine the characteristics and consequences of co-pathologies in neurodegenerative disorders. Additionally, the review will outline emerging therapeutic strategies targeted at restoring proteostasis and mitigating the effects of co-pathological processes associated with neurodegenerative diseases. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chaperone-mediated remodelling of mutant huntingtin. 伴蛋白介导的突变型亨廷顿蛋白的重塑。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0269

Kunal Gharat, Janine Kirstein

引用次数: 0