Frontiers in cell death最新文献

{"title":"Resistance to CLnA-induced ferroptosis is acquired in Caco-2 cells upon differentiation","authors":"Géraldine Cuvelier, Perrine Vermonden, J. Rousseau, O. Féron, R. Rezsohazy, Y. Larondelle","doi":"10.3389/fceld.2023.1219672","DOIUrl":"https://doi.org/10.3389/fceld.2023.1219672","url":null,"abstract":"In contrast to canonical ferroptosis inducers, highly peroxidable conjugated linolenic acids (CLnA) directly fuel the lipid peroxidation cascade upon their incorporation into membrane phospholipids. Little is known, however, about the cytotoxicity level of CLnAs to normal epithelial cells. Caco-2 cells, derived from colorectal adenocarcinoma, spontaneously differentiate into enterocyte-like cells over a period of 21 days of cell culturing, allowing for graduated phenotypic shift from proliferative, undifferentiated cells to a functional intestinal barrier. We exploited this property to assess the sensitivity of Caco-2 cells to CLnAs at different stages of differentiation. Our results show a significant decrease in CLnA-induced ferroptotic cell death over time. The acquired resistance aligned with decreases in cell proliferation and in the extent of lipid peroxidation, as well as with an increase in the expression of GPX4 upon differentiation. These results highlight that while CLnAs are highly toxic for proliferating cancer cells, differentiated epithelial cells are resistant to CLnA-induced ferroptosis. Therefore, this study gives credential to the therapeutic use of CLnAs as an anticancer strategy and offers a new model study to further investigate the safety of peroxidable fatty acids in differentiated cells.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91081004","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}

{"title":"Dissecting the mechanism of regulation of a ferroptosis-like form of cell death in Drosophila melanogaster","authors":"Sanjay Saini, Edward Owusu-Ansah","doi":"10.3389/fceld.2023.1209641","DOIUrl":"https://doi.org/10.3389/fceld.2023.1209641","url":null,"abstract":"Ferroptosis is a specific form of non-apoptotic cell death that is driven by iron-dependent phospholipid peroxidation. Research over the past decade has contributed to our understanding of how this important cell death process is regulated in mammalian systems, especially with regard to the distinct modes of induction, the role of metabolic signals, the organelles involved, implications of ferroptosis for development and aging, and how our improved understanding of the process can be exploited for therapeutic purposes. Other studies have described variants of this ancient cell death process in cyanobacteria, plants and protozoans. Emerging evidence indicates that a ferroptosis-like form of cell death exists in fruit flies (Drosophila melanogaster). Due to the extensive homology of genes in Drosophila melanogaster and Drosophila suzukii, unique aspects of ferroptosis in Drosophila melanogaster may be of particular relevance for developing targeted pesticides against Drosophila suzukii—a major invasive agricultural pest of the berry and wine industry in Southeast Asia, Europe and America. Further, aspects of ferroptosis in Drosophila melanogaster that are conserved in insects in general may provide the basis for identifying new insecticides for controlling the spread of vector-borne diseases such as malaria. In this perspective, we highlight some of the studies in Drosophila melanogaster that have sought to improve our understanding of the ferroptosis-like form of cell death that operates in this organism and conclude with a discussion of the opportunities and challenges for studying this phenomenon in fruit flies.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76954015","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}

{"title":"One-half century (or more) of study of cell death: origins, present, and perhaps future","authors":"R. Lockshin","doi":"10.3389/fceld.2023.1197400","DOIUrl":"https://doi.org/10.3389/fceld.2023.1197400","url":null,"abstract":"The concept of biological cell death—that is, cell death that is neither accidental nor chaotic—has existed and has been obvious since at least the beginning of the 20th C, but it was noticed by other than specialists apt choices of words that caught the spirit of the time, “programmed cell death” and “apoptosis” caught the attention of a wider range of scientists. Then, by the early 1990s the recognition of at least two genes that were important to cancer and other diseases by controlling cell death (p53, Bcl-2, and Fas); recognition that cell death could be controlled by a highly conserved family of proteases; and the development of rapid and easy means of measuring cell death, led to the explosion of the field as a subject of research. Today we recognize many variations on the theme of biological cell death, but many mysteries remain. The most important of these remaining mysteries is that we recognize many of the penultimate and ultimate steps to kill cells, but it is rarely clear how and why these steps are activated. Most likely they are activated by an interaction of several metabolic steps, but we will need more high-powered analysis to determine how this interaction functions.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"14 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72557402","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}

{"title":"Multifaceted promotion of apoptosis by acetylcholinesterase","authors":"Debbra Y. Knorr, D. Demirbas, R. Heinrich","doi":"10.3389/fceld.2023.1169966","DOIUrl":"https://doi.org/10.3389/fceld.2023.1169966","url":null,"abstract":"Elevated expression of acetylcholinesterase (AChE) is a common characteristic of apoptotic cells in both invertebrate and vertebrate species. While increased levels of acetylcholinesterase sensitize cells to apoptogenic stimuli, its absence or pharmacological inactivation interferes with apoptotic cell death. acetylcholinesterase may exert its pro-apoptotic function directly as an integral component of the apoptotic molecular machinery or indirectly by limiting the availability of receptor ligands and structural binding partners that promote cell survival under non-apoptogenic conditions. acetylcholinesterase promotes formation of the apoptosome and degrades DNA after nuclear accumulation. Its esterase activity limits the availability of acetylcholine as ligand for cell membrane-located nicotinic and muscarinic ACh-receptors and mitochondrial nicotinic ACh-receptors that normally support vital physiological states. Studies on insects suggest, that cytokine-activated cell-protective pathways may suppress acetylcholinesterase overexpression under apoptogenic conditions to prevent apoptotic cell death. We provide an overview of studies on various organisms and cell types that summarizes the contribution of acetylcholinesterase to the progress of apoptosis via multiple mechanisms.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77340781","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}

{"title":"Non-lethal roles of the initiator caspase Dronc in Drosophila","authors":"Daniel Domínguez, Yun Fan","doi":"10.3389/fceld.2023.1184041","DOIUrl":"https://doi.org/10.3389/fceld.2023.1184041","url":null,"abstract":"The role of caspases, or cysteine-aspartic proteases, in apoptosis has been well-studied across multiple organisms. These apoptotic caspases can be divided into initiator and effector caspases, with the former cleaving and activating the latter to trigger cell death. However, emerging evidence is supporting non-lethal roles of caspases in development, tissue homeostasis and disease. In comparison to effector caspases, less is known about the non-apoptotic functions of initiator caspases because of their more restricted activities and fewer known substrates. This review focuses on some recent findings in Drosophila on non-lethal roles of the initiator caspase Dronc. We discuss their biological importance, underlying regulatory mechanisms, and implications for our understanding of their mammalian counterparts. Deciphering the non-apoptotic functions of Dronc will provide valuable insights into the multifaceted functions of caspases during development and in diseases including cancer.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83205560","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}

{"title":"From TNF-induced signaling to NADPH oxidase enzyme activity: Methods to investigate protein complexes involved in regulated cell death modalities","authors":"Maria Ladik, Hana Valenta, M. Erard, P. Vandenabeele, Franck B. Riquet","doi":"10.3389/fceld.2023.1127330","DOIUrl":"https://doi.org/10.3389/fceld.2023.1127330","url":null,"abstract":"The formation of molecular complexes is a key feature of intracellular signaling pathways which governs to the initiation and execution of dedicated cellular processes. Tumor Necrosis Factor (TNF) and Reactive Oxygen Species (ROS) function as signaling molecules and are both involved in balancing cell fate decision between cell survival or cell demise. As master regulators of cell signaling, they are also instrumental in controlling various cellular processes towards tissue homeostasis, innate immunity and inflammation. Interestingly, TNF and ROS are interlinked and involved in regulating each other’s production via the engagement of molecular signaling complexes. This relationship calls for detailed reviewing of both TNF-induced and ROS-producing molecular complexes in the context of regulated cell death (RCD) modalities. Here, we outline biotechnological approaches that were used to investigate the TNF- and, concerning ROS, the NADPH oxidase-related molecular complexes with an emphasis on different regulated cell death modalities. This systematic review highlights how the cell death field has benefited from both biochemical and live-cell fluorescence imaging approaches. This knowledge and established workflows are highly generalizable, can be of a broader use for any protein-complex studies, and well suited for addressing new challenges in signaling dynamics. These will help understand molecular signaling complexes as ensembles organized into signaling platforms, most likely the key sites of signaling dynamics integration toward cell fate regulation.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75368004","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}

{"title":"Regulators mount up: the metabolic roles of apoptotic proteins.","authors":"James H Schofield, Zachary T Schafer","doi":"10.3389/fceld.2023.1223926","DOIUrl":"10.3389/fceld.2023.1223926","url":null,"abstract":"<p><p>The induction of apoptosis, a programmed cell death pathway governed by activation of caspases, can result in fundamental changes in metabolism that either facilitate or restrict the execution of cell death. In addition, metabolic adaptations can significantly impact whether cells in fact initiate the apoptotic cascade. In this mini-review, we will highlight and discuss the interconnectedness of apoptotic regulation and metabolic alterations, two biological outcomes whose regulators are intertwined.</p>","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916139","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}

{"title":"Biophysics at the edge of life and death: radical control of apoptotic mechanisms.","authors":"Samantha J Hack, Wendy S Beane, Kelly Ai-Sun Tseng","doi":"10.3389/fceld.2023.1147605","DOIUrl":"10.3389/fceld.2023.1147605","url":null,"abstract":"<p><p>Recent studies have furthered our understanding of how dying and living cells interact in different physiological contexts, however the signaling that initiates and mediates apoptosis and apoptosis-induced proliferation are more complex than previously thought. One increasingly important area of study is the biophysical control of apoptosis. In addition to biochemical regulation, biophysical signals (including redox chemistry, bioelectric gradients, acoustic and magnetic stimuli) are also known yet understudied regulators of both cell death and apoptosis-induced proliferation. Mounting evidence suggests biophysical signals may be key targets for therapeutic interventions. This review highlights what is known about the role of biophysical signals in controlling cell death mechanisms during development, regeneration, and carcinogenesis. Since biophysical signals can be controlled spatiotemporally, bypassing the need for genetic manipulation, further investigation may lead to fine-tuned modulation of apoptotic pathways to direct desired therapeutic outcomes.</p>","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86599346","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}

{"title":"Model systems in cell death-grand challenge","authors":"L. Schwartz","doi":"10.3389/fceld.2022.1087903","DOIUrl":"https://doi.org/10.3389/fceld.2022.1087903","url":null,"abstract":"In 1929, the Nobel Prize winning physiologist August Krough observed that “For a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied.” (Krogh, 1929). Known as the Krough Principal, this appreciation of a “model systems” approach has been foundational for many aspects of basic biology, from the use of the squid giant axon to define the ionic basis of the action potential to the use of the fruit fly to unlock the molecular basis of biological clocks. While the ultimate goal for many researchers may be to gain a better understanding of human development and/or pathogenesis, the complexity of mammalian systems often makes direct analyses challenging. Invertebrates and other “simpler”model systems often display adaptations that exaggerate normal cellular processes that make them attractive vehicles for the analysis of specific traits. This approach has also proven to be foundational for the study of cell death. The term “programmed cell death” (PCD) (now commonly referred to as “regulated cell death” to distinguish it from “accidental cell death” (Galluzzi et al., 2018)) was coined by Lockshin andWilliams in 1965 to describe the precisely timed loss of the intersegmental muscles of Lepidoptera at the end of metamorphosis (Lockshin and Williams, 1965). These giant cells (each of which is ~5 mm long and up to 1 mm in diameter depending on the species) initiate PCD coincident with the emergence of the adult moth from the overlying pupal cuticle. Few other naturally occurring examples of PCD are so exquisitely timed or offer such prodigious amounts of clean cellular material for molecular and biochemical analyses (e.g., Tsuji et al., 2020). However, it was another invertebrate model, the nematode Caenorhabditis elegans, that propelled the field of cell death from a small cottage industry with a few dozen investigators in the 1970s and 1980s into a massive research enterprise that has produced more than 560,000 publications during the past 30 years. One of the unique features of C. elegans that make it such an attractive model is that it displays “cell consistency”, meaning that every individual has the same number of somatic cells. By performing detailed lineage analyses, the identity and fate of every single cell was described by Sulston and Horvitz (Sulston and Horvitz, 1977). For about 20% of the cells, their fate is to die, primarily via apoptosis. At the time this work was conducted it was not well understood if PCD during development reflected the simple wasting away of surplus/unnecessary cells, active murder by neighboring cells, or cell-autonomous suicide. Using a clever genetic trick that prevented dying cells from being phagocytosed and thus rapidly removed, the Horvitz lab demonstrated that the ability of cells to die required the activity of specific genes that acted in a cell autonomous manner, and thus represented OPEN ACCESS","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77728595","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}