scholarly journals Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ling Huang ◽  
Daniel B. McClatchy ◽  
Pamela Maher ◽  
Zhibin Liang ◽  
Jolene K. Diedrich ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Model ◽  
Early Stage ◽  
Metabolic Reprogramming ◽  
Therapeutic Interventions ◽  
Amyloid Toxicity ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
Metabolomic Data ◽  
Basic Biology

Abstract Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.

scholarly journals Implication of the oep16-1 Mutation in a flu-Independent, Singlet Oxygen-Regulated Cell Death Pathway in Arabidopsis thaliana

2010 ◽  
Vol 52 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Iga Samol ◽  
Frank Buhr ◽  
Armin Springer ◽  
Stephan Pollmann ◽  
Abder Lahroussi ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cell Death ◽  
Singlet Oxygen ◽  
Cell Death Pathway ◽  
Regulated Cell Death

scholarly journals Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death

2020 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Plant Life ◽  
Regulated Cell Death ◽  
Dependent Cell ◽  
Plant Life Cycle ◽  
High Degree

Abstract Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.

scholarly journals Discovery and molecular characterization of a Bcl-2-regulated cell death pathway in schistosomes

2011 ◽  
Vol 108 (17) ◽  
pp. 6999-7003 ◽  
Author(s):  
E. F. Lee ◽  
O. B. Clarke ◽  
M. Evangelista ◽  
Z. Feng ◽  
T. P. Speed ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Characterization ◽  
Cell Death Pathway ◽  
Regulated Cell Death

scholarly journals Gene expression profile analysis of gallic acid-induced cell death process

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ho Man Tang ◽  
Peter Chi Keung Cheung
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Gallic Acid ◽  
Time Course ◽  
Early Stage ◽  
Expression Profiles ◽  
Death Process ◽  
Apoptotic Pathway ◽  
Cell Death Pathway ◽  
Cell Death Process

AbstractGallic acid is a natural phenolic compound that displays anti-cancer properties in clinically relevant cell culture and rodent models. To date, the molecular mechanism governing the gallic acid-induced cancer cell death process is largely unclear, thus hindering development of novel therapeutics. Therefore, we performed time-course RNA-sequencing to reveal the gene expression profiles at the early (2nd hour), middle (4th and 6th hour), and late (9th hour) stages of the gallic acid-induced cell death process in HeLa cells. By Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we found significant changes in transcription of the genes in different types of cell death pathways. This involved the ferroptotic cell death pathway at the early stage, apoptotic pathway at the middle stage, and necroptotic pathway at the late stage. Metabolic pathways were identified at all the stages, indicating that this is an active cell death process. Interestingly, the initiation and execution of gallic acid-induced cell death were mediated by multiple biological processes, including iron and amino acid metabolism, and the biosynthesis of glutathione, as targeting on these pathways suppressed cell death. In summary, our work provides a dataset with differentially expressed genes across different stages of cell death process during the gallic acid induction, which is important for further study on the control of this cell death mechanism.

scholarly journals Heat stress induces ferroptosis in a photosynthetic prokaryote

2019 ◽  
Author(s):  
Anabella Aguilera ◽  
Federico Berdun ◽  
Carlos Bartoli ◽  
Charlotte Steelheart ◽  
Matías Alegre ◽  
...  
Keyword(s):  
Cell Death ◽  
Heat Stress ◽  
Similar Process ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
Cell Death Program ◽  
Dependent Form ◽  
A Cell ◽  
Eukaryotic Organisms ◽  
Pcc 6803

AbstractFerroptosis is an oxidative iron-dependent form of cell death recently described in eukaryotic organisms like animals, plants and parasites. Here we report that a similar process takes place in the cyanobacterium Synechocystis sp. PCC 6803 in response to heat stress. After a heat shock, Synechocystis cells undergo a cell death pathway that can be suppressed by canonical ferroptosis inhibitors or by external addition of calcium, glutathione or ascorbic acid. Moreover, as described for eukaryotic cells ferroptosis, this pathway is characterized by an early depletion of antioxidants, and by lipid peroxidation. As in general prokaryotes membranes contain poorly oxidizable saturated or monounsaturated lipid molecules, it was thought that they were not susceptible to ferroptosis. Interestingly, cyanobacteria contain thylakoid membranes that are enriched in polyunsaturated-fatty-acid-containing phospholipids, which might explain their sensitivity to ferroptosis. These results indicate that all of the hallmarks described for eukaryotic ferroptosis are conserved in photosynthetic prokaryotes and suggest that ferroptosis might be an ancient cell death program.SummaryAguilera et al, show that ferroptosis, an oxidative and iron-dependent form of regulated cell death, plays an important role in the cyanobacterium Synechocystis sp. PCC 6803 in response to heat stress.

scholarly journals The Impact of Autophagy on Cell Death Modalities

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Stefan W. Ryter ◽  
Kenji Mizumura ◽  
Augustine M. K. Choi
Keyword(s):  
Cell Death ◽  
Inflammatory Responses ◽  
Degradation Pathway ◽  
Therapeutic Interventions ◽  
Caspase 1 ◽  
Regulated Cell Death ◽  
Caspase Inhibition ◽  
Autophagic Degradation ◽  
Dependent Cell ◽  
The Impact

Autophagy represents a homeostatic cellular mechanism for the turnover of organelles and proteins, through a lysosome-dependent degradation pathway. During starvation, autophagy facilitates cell survival through the recycling of metabolic precursors. Additionally, autophagy can modulate other vital processes such as programmed cell death (e.g., apoptosis), inflammation, and adaptive immune mechanisms and thereby influence disease pathogenesis. Selective pathways can target distinct cargoes (e.g., mitochondria and proteins) for autophagic degradation. At present, the causal relationship between autophagy and various forms of regulated or nonregulated cell death remains unclear. Autophagy can occur in association with necrosis-like cell death triggered by caspase inhibition. Autophagy and apoptosis have been shown to be coincident or antagonistic, depending on experimental context, and share cross-talk between signal transduction elements. Autophagy may modulate the outcome of other regulated forms of cell death such as necroptosis. Recent advances suggest that autophagy can dampen inflammatory responses, including inflammasome-dependent caspase-1 activation and maturation of proinflammatory cytokines. Autophagy may also act as regulator of caspase-1 dependent cell death (pyroptosis). Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases in which apoptosis or other forms of regulated cell death may play a cardinal role.

scholarly journals Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Cliff J. Luke ◽  
Stephanie Markovina ◽  
Misty Good ◽  
Ira E. Wight ◽  
Brian J. Thomas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cathepsin L ◽  
Cysteine Protease Inhibitor ◽  
C Elegans ◽  
Cell Death Pathways ◽  
Cell Death Pathway ◽  
Endogenous Inhibitors ◽  
Regulated Cell Death ◽  
Evolutionarily Conserved ◽  
Dependent Cell

AbstractLysosomal membrane permeabilization (LMP) and cathepsin release typifies lysosome-dependent cell death (LDCD). However, LMP occurs in most regulated cell death programs suggesting LDCD is not an independent cell death pathway, but is conscripted to facilitate the final cellular demise by other cell death routines. Previously, we demonstrated that Caenorhabditis elegans (C. elegans) null for a cysteine protease inhibitor, srp-6, undergo a specific LDCD pathway characterized by LMP and cathepsin-dependent cytoplasmic proteolysis. We designated this cell death routine, lysoptosis, to distinguish it from other pathways employing LMP. In this study, mouse and human epithelial cells lacking srp-6 homologues, mSerpinb3a and SERPINB3, respectively, demonstrated a lysoptosis phenotype distinct from other cell death pathways. Like in C. elegans, this pathway depended on LMP and released cathepsins, predominantly cathepsin L. These studies suggested that lysoptosis is an evolutionarily-conserved eukaryotic LDCD that predominates in the absence of neutralizing endogenous inhibitors.

scholarly journals Cytosolic Acidification Is the First Transduction Signal of Lactoferrin-induced Regulated Cell Death Pathway

2019 ◽  
Vol 20 (23) ◽  
pp. 5838 ◽  
Author(s):  
Andrés ◽  
Acosta-Zaldívar ◽  
González-Seisdedos ◽  
Fierro
Keyword(s):  
Cell Death ◽  
Critical Role ◽  
K Channel ◽  
Antimicrobial Protein ◽  
Channel Blockers ◽  
Cytosolic Ph ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
Transduction Signal ◽  
Cytosolic Acidification

In yeast, we reported the critical role of K+-efflux for the progress of the regulated cell death (RCD) induced by human lactoferrin (hLf), an antimicrobial protein of the innate immune system that blocks Pma1p H+-ATPase. In the present study, the K+ channel Tok1p was identified as the K+ channel-mediating K+-efflux, as indicated by the protective effect of extracellular K+ (30 mM), K+-channel blockers, and the greater hLf-resistance of TOK1-disrupted strains. K+-depletion was necessary but not sufficient to induce RCD as inferred from the effects of valinomycin, NH4Cl or nigericin which released a percentage of K+ similar to that released by lactoferrin without affecting cell viability. Cytosolic pH of hLf-treated cells decreased transiently (0.3 pH units) and its inhibition prevented the RCD process, indicating that cytosolic acidification was a necessary and sufficient triggering signal. The blocking effect of lactoferrin on Pma1p H+-ATPase caused a transitory decrease of cytosolic pH, and the subsequent membrane depolarization activated the voltage-gated K+ channel, Tok1p, allowing an electrogenic K+-efflux. These ionic events, cytosolic accumulation of H+ followed by K+-efflux, constituted the initiating signals of this mitochondria-mediated cell death. These findings suggest, for the first time, the existence of an ionic signaling pathway in RCD.

C-ferroptosis is an iron-dependent form of regulated cell death in cyanobacteria

2021 ◽  
Vol 221 (2) ◽  
Author(s):  
Anabella Aguilera ◽  
Federico Berdun ◽  
Carlos Bartoli ◽  
Charlotte Steelheart ◽  
Matías Alegre ◽  
...  
Keyword(s):  
Cell Death ◽  
Similar Process ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
Cell Death Program ◽  
Dependent Form ◽  
A Cell ◽  
Eukaryotic Organisms ◽  
Synechocystis Sp ◽  
Pcc 6803

Ferroptosis is an oxidative and iron-dependent form of regulated cell death (RCD) recently described in eukaryotic organisms like animals, plants, and parasites. Here, we report that a similar process takes place in the photosynthetic prokaryote Synechocystis sp. PCC 6803 in response to heat stress. After a heat shock, Synechocystis sp. PCC 6803 cells undergo a cell death pathway that can be suppressed by the canonical ferroptosis inhibitors, CPX, vitamin E, Fer-1, liproxstatin-1, glutathione (GSH), or ascorbic acid (AsA). Moreover, as described for eukaryotic ferroptosis, this pathway is characterized by an early depletion of the antioxidants GSH and AsA, and by lipid peroxidation. These results indicate that all of the hallmarks described for eukaryotic ferroptosis are conserved in photosynthetic prokaryotes and suggest that ferroptosis might be an ancient cell death program.

scholarly journals Induction and application of ferroptosis in cancer therapy

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Qing Nie ◽  
Yue Hu ◽  
Xiao Yu ◽  
Xiao Li ◽  
Xuedong Fang
Keyword(s):  
Cell Death ◽  
Tumor Therapy ◽  
Tumor Biology ◽  
Materials Chemistry ◽  
Tumor Cell Death ◽  
Redox Biology ◽  
Cell Death Pathways ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
New Ideas

AbstractAt present, more than one cell death pathways have been found, one of which is ferroptosis. Ferroptosis was discovered in 2012 and described as an iron-dependent and lipid peroxidation-driven regulated cell death pathway. In the past few years, ferroptosis has been shown to induce tumor cell death, providing new ideas for tumor treatment. In this article, we summarize the latest advances in ferroptosis-induced tumor therapy at the intersection of tumor biology, molecular biology, redox biology, and materials chemistry. First, we state the characteristics of ferroptosis in cells, then introduce the key molecular mechanism of ferroptosis, and describes the relationship between ferroptosis and oxidative stress signaling pathways. Finally, we focused on several types of ferroptosis inducers discovered by scholars, and the application of ferroptosis in systemic chemotherapy, radiotherapy, immunotherapy and nanomedicine, in the hope that ferroptosis can exert its potential in the treatment of tumors.

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