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

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.

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

Journal of Experimental Botany ◽

10.1093/jxb/eraa425 ◽

2020 ◽

Cited By ~ 1

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.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1100652108 ◽

2011 ◽

Vol 108 (17) ◽

pp. 6999-7003 ◽

Cited By ~ 38

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

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Plastid mediated Singlet Oxygen in Regulated Cell Death

Plant Biology ◽

10.1111/plb.13260 ◽

2021 ◽

Author(s):

Mansi Bhatt ◽

Shiv Shanker Pandey ◽

Anand Krishna Tiwari ◽

Budhi Sagar Tiwari

Keyword(s):

Cell Death ◽

Singlet Oxygen ◽

Regulated Cell Death

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Heat stress induces ferroptosis in a photosynthetic prokaryote

10.1101/828293 ◽

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.

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Singlet oxygen triggers chloroplast rupture and cell death in the zeaxanthin epoxidase defective mutant aba1 of Arabidopsis thaliana under high light stress

Journal of Plant Physiology ◽

10.1016/j.jplph.2017.06.009 ◽

2017 ◽

Vol 216 ◽

pp. 188-196 ◽

Cited By ~ 2

Author(s):

Álvaro Sánchez-Corrionero ◽

Inmaculada Sánchez-Vicente ◽

Sergio González-Pérez ◽

Ascensión Corrales ◽

Anja Krieger-Liszkay ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Cell Death ◽

Singlet Oxygen ◽

Light Stress ◽

High Light ◽

Zeaxanthin Epoxidase ◽

High Light Stress ◽

Defective Mutant

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

Communications Biology ◽

10.1038/s42003-021-02953-x ◽

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20235838 ◽

2019 ◽

Vol 20 (23) ◽

pp. 5838 ◽

Cited By ~ 2

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.

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

The Journal of Cell Biology ◽

10.1083/jcb.201911005 ◽

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.

Download Full-text