Pub Date : 2023-04-17DOI: 10.3389/fceld.2023.1169966
Debbra Y. Knorr, D. Demirbas, R. Heinrich
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.
{"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}
Pub Date : 2023-04-06DOI: 10.3389/fceld.2023.1184041
Daniel Domínguez, Yun Fan
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.
{"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}
Pub Date : 2023-04-05DOI: 10.3389/fceld.2023.1127330
Maria Ladik, Hana Valenta, M. Erard, P. Vandenabeele, Franck B. Riquet
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.
{"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}
Pub Date : 2023-02-27DOI: 10.3389/fceld.2023.1147605
Samantha J. Hack, Wendy S. Beane, K. Tseng
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.
{"title":"Biophysics at the edge of life and death: Radical control of apoptotic mechanisms","authors":"Samantha J. Hack, Wendy S. Beane, K. Tseng","doi":"10.3389/fceld.2023.1147605","DOIUrl":"https://doi.org/10.3389/fceld.2023.1147605","url":null,"abstract":"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.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86599346","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}
Pub Date : 2023-01-01Epub Date: 2023-07-03DOI: 10.3389/fceld.2023.1223926
James H Schofield, Zachary T Schafer
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.
{"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}
Pub Date : 2022-12-05DOI: 10.3389/fceld.2022.1087903
L. Schwartz
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
1929年，诺贝尔奖得主、生理学家奥古斯特·克拉夫(August Krough)观察到:“对于许多问题，总会有一些或少数动物可供选择，它们是最方便研究的对象。”(克拉夫，1929)。这种对“模型系统”方法的欣赏被称为克拉夫原理，它已经成为基础生物学许多方面的基础，从使用鱿鱼巨大轴突来定义动作电位的离子基础到使用果蝇来解锁生物钟的分子基础。虽然许多研究人员的最终目标可能是更好地了解人类发育和/或发病机制，但哺乳动物系统的复杂性往往使直接分析具有挑战性。无脊椎动物和其他“更简单”的模型系统经常表现出夸大正常细胞过程的适应性，这使它们成为分析特定特征的有吸引力的工具。这种方法也被证明是研究细胞死亡的基础。术语“程序性细胞死亡”(PCD)(现在通常被称为“调节细胞死亡”，以区别于“意外细胞死亡”(Galluzzi等人，2018))是由Lockshin和Williams在1965年创造的，用于描述鳞翅目动物在变态结束时节间肌肉的精确时间损失(Lockshin和Williams, 1965)。这些巨细胞(每个约5毫米长，直径可达1毫米，取决于物种)在成蛾从上面的蛹角质层出现的同时启动PCD。很少有其他自然发生的PCD例子如此精确地定时或提供如此大量的清洁细胞材料用于分子和生化分析(例如，Tsuji et al.， 2020)。然而，是另一种无脊椎动物模型——隐杆线虫，推动了细胞死亡领域从20世纪70年代和80年代的几十名研究人员的小型家庭手工业发展成为一个庞大的研究企业，在过去的30年里发表了56万多篇论文。秀丽隐杆线虫的一个独特特征使它成为一个如此吸引人的模型，它表现出“细胞一致性”，这意味着每个个体都有相同数量的体细胞。通过进行详细的谱系分析，Sulston和Horvitz描述了每个单细胞的身份和命运(Sulston和Horvitz, 1977)。对于大约20%的细胞，它们的命运是死亡，主要是通过凋亡。在进行这项工作的时候，人们还不太清楚发育过程中的PCD是否反映了多余/不必要细胞的简单浪费，邻近细胞的主动谋杀，或细胞自主自杀。霍维茨实验室利用一种巧妙的基因技巧，阻止垂死的细胞被吞噬，从而迅速被清除，证明细胞死亡的能力需要特定基因的活性，这些基因以细胞自主的方式起作用，因此代表了开放获取
{"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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：