Ferroptosis-like death in plant cells

Conlon, Megan; Dixon, Scott J.

doi:10.1080/23723556.2017.1302906

Cited by 12 publications

(11 citation statements)

References 10 publications

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“…Not only is ferroptosis proving important for the regulation of cancer cell death (Shen et al, 2018) and the pathophysiology of neurodegenerative disorders (Hambright et al, 2017;Morris et al, 2018), the broad significance of this pathway has recently been established through observations of root cells in response to heat shock in the flowering plant Arabidopsis thaliana (Distéfano et al, 2017). The similarity of this GPX4-mediated cell decline in animal and plant cells (Conlon and Dixon, 2017) alludes to the possibility that ferroptosis may be a highly conserved mechanism to respond to acute stress that is evolutionarily ancient, though only recently characterized (Distéfano et al, 2017;Conrad et al, 2018). Building on these discoveries, here we present the first findings of ferroptosis outside of the soma, and provide evidence for the exclusivity of this process to the round spermatid stage of testicular sperm development.…”

Section: Discussionmentioning

confidence: 99%

Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids

Bromfield

Walters

Cafe

et al. 2019

MHR: Basic Science of Reproductive Medicine

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Oxidative stress is a major aetiology in many pathologies, including that of male infertility. Recent evidence in somatic cells has linked oxidative stress to the induction of a novel cell death modality termed ferroptosis. However, the induction of this iron-regulated, caspase-independent cell death pathway has never been explored outside of the soma. Ferroptosis is initiated through the inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and is exacerbated by the activity of arachidonate 15-lipoxygenase (ALOX15), a lipoxygenase enzyme that facilitates lipid degradation. Here, we demonstrate that male germ cells of the mouse exhibit hallmarks of ferroptosis including; a caspaseindependent decline in viability following exposure to oxidative stress conditions induced by the electrophile 4-hydroxynonenal or the ferroptosis activators (erastin and RSL3), as well as a reciprocal upregulation of ALOX15 and down regulation of GPX4 protein expression. Moreover, the round spermatid developmental stage may be sensitized to ferroptosis via the action of acyl-CoA synthetase long-chain family member 4 (ACSL4), which modifies membrane lipid composition in a manner favourable to lipid peroxidation. This work provides a clear impetus to explore the contribution of ferroptosis to the demise of germline cells during periods of acute stress in in vivo models.

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Section: Discussionmentioning

confidence: 99%

Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids

Bromfield

Walters

Cafe

et al. 2019

MHR: Basic Science of Reproductive Medicine

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“…In both heatshocked root hairs and the hypersensitive response, models for interpretation of the results show dependence of ferroptosis on iron and glutathione and include one or more Gpx4 orthologues. Inhibition of these peroxidases or depletion of GSH is suggested to trigger ferroptosis (Conlon and Dixon 2017;Dangol et al 2019). It is important to consider, however, that, in contrast to HsGpx4, the non-SeC plant GPXLs are not reduced by GSH but rather employ TRXs as electron donor (see Paradigm shift 6).…”

Section: Paradigm Shift 4: Thiol Peroxidases Link Ros To Functional Rmentioning

confidence: 99%

Shifting paradigms and novel players in Cys-based redox regulation and ROS signaling in plants - and where to go next

Meyer

Dreyer

Ugalde

et al. 2020

Biological Chemistry

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Cys-based redox regulation was long regarded a major adjustment mechanism of photosynthesis and metabolism in plants, but in the recent years, its scope has broadened to most fundamental processes of plant life. Drivers of the recent surge in new insights into plant redox regulation have been the availability of the genome-scale information combined with technological advances such as quantitative redox proteomics and in vivo biosensing. Several unexpected findings have started to shift paradigms of redox regulation. Here, we elaborate on a selection of recent advancements, and pinpoint emerging areas and questions of redox biology in plants. We highlight the significance of (1) proactive H2O2 generation, (2) the chloroplast as a unique redox site, (3) specificity in thioredoxin complexity, (4) how to oxidize redox switches, (5) governance principles of the redox network, (6) glutathione peroxidase-like proteins, (7) ferroptosis, (8) oxidative protein folding in the ER for phytohormonal regulation, (9) the apoplast as an unchartered redox frontier, (10) redox regulation of respiration, (11) redox transitions in seed germination and (12) the mitochondria as potential new players in reductive stress safeguarding. Our emerging understanding in plants may serve as a blueprint to scrutinize principles of reactive oxygen and Cys-based redox regulation across organisms.

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“…A similar phenotype was observed in an Arabidopsis AtPYE T-DNA insertion line, which demonstrated poor tolerance to Fe deficiency and elevated tissue Fe concentrations relative to WT plants [16]. Under conditions of excess Fe, reactive oxygen species (ROS) accumulate due to the Fenton reaction and can lead to Fe-toxicity-mediated PCD (also known as ferroptosis) [31,32]. Previous hydroponic Fe deficiency experiments demonstrated significantly higher shoot Fe concentration, shoot ROS concentrations, and activity of OsNAC4 (a TF that regulates PCD) in iro3 mutants relative to WT plants [24,25,33].…”

Section: Discussionmentioning

confidence: 64%

A Model to Incorporate the bHLH Transcription Factor OsIRO3 within the Rice Iron Homeostasis Regulatory Network

Carey-Fung

O’Brien

Beasley

et al. 2022

IJMS

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Iron (Fe) homeostasis in plants is governed by a complex network of regulatory elements and transcription factors (TFs), as both Fe toxicity and deficiency negatively impact plant growth and physiology. The Fe homeostasis network is well characterized in Arabidopsis thaliana and remains poorly understood in monocotyledon species such as rice (Oryza sativa L.). Recent investigation of the rice Fe homeostasis network revealed OsIRO3, a basic Helix–Loop–Helix (bHLH) TF as a putative negative regulator of genes involved in Fe uptake, transport, and storage. We employed CRISPR-Cas9 gene editing to target the OsIRO3 coding sequence and generate two independent T-DNA-free, loss-of-function iro3 mutants in rice cv. Nipponbare. The iro3 mutant plants had similar phenotype under nutrient-sufficient conditions and had stunted growth under Fe-deficient conditions, relative to a T-DNA free, wild-type control (WT). Under Fe deficiency, iro3 mutant shoots had reduced expression of Fe chelator biosynthetic genes (OsNAS1, OsNAS2, and OsNAAT1) and upregulated expression of an Fe transporter gene (OsYSL15), relative to WT shoots. We place our results in the context of the existing literature and generate a model describing the role of OsIRO3 in rice Fe homeostasis and reinforce the essential function of OsIRO3 in the rice Fe deficiency response.

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Ferroptosis-like death in plant cells

Cited by 12 publications

References 10 publications

Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids

Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids

Shifting paradigms and novel players in Cys-based redox regulation and ROS signaling in plants - and where to go next

A Model to Incorporate the bHLH Transcription Factor OsIRO3 within the Rice Iron Homeostasis Regulatory Network

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