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

Regulated cell death plays key roles during essential processes along the plant life cycle. It takes part of specific developmental programs and maintains the organism homeostasis in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. Ferroptosis in plants shares all the main hallmarks described for ferroptosis in other systems. Those specific features include biochemical and morphological signatures that seem 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, main players and underlying pathways.Fil: Distefano, Ayelen Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Lopez, Gabriel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Setzes, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Marchetti, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Cainzos Gelabert, Maximiliano Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Cascallares, María Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Zabaleta, Eduardo Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Pagnussat, Gabriela Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentin

Investigating the cell and developmental biology of plant infection by the rice blast fungus Magnaporthe oryzae

Magnaporthe oryzae is the causal agent of rice blast disease, the most widespread and serious disease of cultivated rice. Live cell imaging and quantitative 4D image analysis have provided new insight into the mechanisms by which the fungus infects host cells and spreads rapidly in plant tissue. In this video review article, we apply live cell imaging approaches to understanding the cell and developmental biology of rice blast disease. To gain entry to host plants, M. oryzae develops a specialised infection structure called an appressorium, a unicellular dome-shaped cell which generates enormous turgor, translated into mechanical force to rupture the leaf cuticle. Appressorium development is induced by perception of the hydrophobic leaf surface and nutrient deprivation. Cargo-independent autophagy in the three-celled conidium, controlled by cell cycle regulation, is essential for appressorium morphogenesis. Appressorium maturation involves turgor generation and melanin pigment deposition in the appressorial cell wall. Once a threshold of turgor has been reached, this triggers re-polarisation which requires regulated generation of reactive oxygen species, to facilitate septin GTPase-dependent cytoskeletal re-organisation and re-polarisation of the appressorium to form a narrow, rigid penetration peg. Infection of host tissue requires a further morphogenetic transition to a pseudohyphal-type of growth within colonised rice cells. At the same time the fungus secretes an arsenal of effector proteins to suppress plant immunity. Many effectors are secreted into host cells directly, which involves a specific secretory pathway and a specialised structure called the biotrophic interfacial complex. Cell-to-cell spread of the fungus then requires development of a specialised structure, the transpressorium, that is used to traverse pit field sites, allowing the fungus to maintain host cell membrane integrity as new living plant cells are invaded. Thereafter, the fungus rapidly moves through plant tissue and host cells begin to die, as the fungus switches to necrotrophic growth and disease symptoms develop. These morphogenetic transitions are reviewed in the context of live cell imaging studies

Recent development on plant aldehyde dehydrogenase enzymes and their functions in plant development and stress signaling

Abstract: Abiotic and biotic stresses induce the formation of reactive oxygen species (ROS), which subsequently causes the excessive accumulation of aldehydes in cells. Stress-derived aldehydes are commonly designated as reactive electrophile species (RES) as a result of the presence of an electrophilicα,β-unsaturated carbonyl group. Aldehyde dehydrogenases (ALDHs) are NAD(P)+-dependent enzymes that metabolize a wide range of endogenous and exogenous aliphatic and aromatic aldehyde molecules by oxidizing them to their corresponding carboxylic acids. The ALDH enzymes are found in nearly all organisms, and plants contain fourteen ALDH protein families. In this review, we performed a critical analysis of the research reports over the last decade on plant ALDHs. Newly discovered roles for these enzymes in metabolism, signaling and development have been highlighted and discussed. We concluded with suggestions for future investigations to exploit the potential of these enzymes in biotechnology and to improve our current knowledge about these enzymes in gene signaling and plant development

Novel Functions Of Cardiolipin Remodeling In Saccharomyces Cerevisiae And Mammalian Cells: Implications For Barth Syndrome

Cardiolipin (CL) is a unique phospholipid that is primarily localized within the inner mitochondrial membrane. Newly synthesized CL undergoes acyl remodeling to produce CL species enriched with unsaturated acyl groups. The tafazzin gene (TAZ) encodes a transacylase that remodels CL. Deficiencies in CL remodeling cause Barth syndrome (BTHS), an X-linked genetic disorder resulting from TAZ mutations that lead to reduced total CL content and an accumulation of monolysocardiolipin (MLCL), an intermediate of the CL remodeling pathway. However, which of these biochemical outcomes contributes to the physiological defects is not fully understood. Deletion of yeast CL phospholipase rescues the taz1growth phenotype. We concluded that an increased MLCL/CL, but not decreased CL unsaturation, is likely the primary cause of decreased respiratory growth and chronological life span observed in taz1. This suggests that the physiological defects of BTHS patients is possibly due to increased MLCL/CL ratio instead of decreased unsaturated CL, and that attenuation of CL phospholipases may potentially treat BTHS. Furthermore, our findings suggested a possibility that CLD1 expression is upregulated in response to oxidative stress. CL peroxidation, resulting from oxidative stress, has been described in mammalian cells. Based on this, one of the physiological roles of CL remodeling is to remove peroxidized CL. Liquid chromatography−mass-spectrometry-based phospholipidomics was combined with genetic and nutritional manipulations to assay CL incorporation of PUFA during the CL biosynthetic and post-synthetic remodeling processes in yeast. Our results demonstrated that yeast readily incorporate PUFA to synthesize oxidizable CL. Although multiple CL-hydroperoxides and CL-dihydroperoxides were readily detected in these cells, cell growth and life span were not impacted. cld1Δ cells expressing ∆12-desaturase were utilized to determine the effect of peroxidation on CL remodeling. Using this novel yeast model, in which cells expressed ∆12-desaturase, the specificity of Cld1 to peroxidized CL, and its role in deacylating peroxidized CL, was determined. In cells expressing desaturase, loss of CLD1 led to increased peroxidized CL species, as well as decreased cell growth and life span. The findings from this study may contribute to our understanding of CL remodeling and its mechanistic roles in mitigating oxidative stress. To probe defects resulting from CL deficiency in mammalian cells, I constructed a tafazzin knockout C2C12 cell line, which exhibits an increased MLCL/CL ratio, decreased respiration capacity, increased ROS generation and decreased membrane potential. Although WT and TAZ-KO C2C12 cells can differentiate into myotubes, differentiation was significantly decreased in TAZ-KO C2C12 cells under certain conditions. Taken together, these findings indicate that CL remodeling plays a role in myotube differentiation

Cell Death, Inflammation and Oxidative Stress in Neurodegenerative Diseases

Neurogenerative diseases encompass very different pathologies, which can be demyelinating or nondemyelinating, but which have common mechanisms such as cell death, oxidative stress and inflammation. A better understanding of these mechanisms allows the search for biomarkers and targets for new therapies. This special issue brings together different data on Alzheimer's disease, Parkinson's disease, and multiple sclerosis, detailing the mechanisms of cell death (necroptosis, ferroptosis), oxidative stress and inflammation but also the possibilities of neuroprotection via 5 research articles and 6 review articles. The different reviews allow us to take stock of cell death, oxidative stress and neuroinflammation in the context of neurodegenerative diseases but also in relation to other pathologies where these processes are involved

Marine Anti-inflammatory and Antioxidant Agents 2021

The Special Issue “Marine Anti-Inflammatory and Antioxidants Agents 2021” collected the latest research, both in vitro and in vivo, on natural compounds from a variety of deep-sea organisms with anti-inflammatory and/or antioxidant properties as potential candidates for new drug discovery, and more generally for the field of marine biotechnology. The research presented here discusses the potential benefits of certain peptides and proteins derived from oysters, blue mussels, and cyanobacteria, as well as the carotenoid pigment astaxanthin, which is found in a variety of marine organisms. This Special Issue has carved out an important space for crude extracts from marine products, such as microalgae and green algae, highlighting their potential benefits to human health. Finally, the Special Issue includes a review of the benefits of some natural compounds derived from the algal biome against inflammatory bowel diseases, as well as a research article identifying the presence of the OvoA gene in arthropods for the first time. Through an excursus of high-quality research, this Special Issue provides the entire scientific community with new tools and insights to catch a molecular treasure for human health from the sea

Acute Hypoxia Alters Extracellular Vesicle Signatures and the Brain Citrullinome of Naked Mole-Rats (Heterocephalus glaber)

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and related to hypoxia. While these markers have been studied in hypoxia-intolerant mammals, in vivo investigations in hypoxia-tolerant species are lacking. Naked mole-rats (NMR) are among the most hypoxia-tolerant mammals and are thus a good model organism for understanding natural and beneficial adaptations to hypoxia. Thus, we aimed to reveal CNS related roles for PADs in hypoxia tolerance and identify whether circulating EV signatures may reveal a fingerprint for adaptive whole-body hypoxia responses in this species. We found that following in vivo acute hypoxia, NMR: (1) plasma-EVs were remodelled, (2) whole proteome EV cargo contained more protein hits (including citrullinated proteins) and a higher number of associated KEGG pathways relating to the total proteome of plasma-EVs Also, (3) brains had a trend for elevation in PAD1, PAD3 and PAD6 protein expression, while PAD2 and PAD4 were reduced, while (4) the brain citrullinome had a considerable increase in deiminated protein hits with hypoxia (1222 vs. 852 hits in normoxia). Our findings indicate that circulating EV signatures are modified and proteomic content is reduced in hypoxic conditions in naked mole-rats, including the circulating EV citrullinome, while the brain citrullinome is elevated and modulated in response to hypoxia. This was further reflected in elevation of some PADs in the brain tissue following acute hypoxia treatment. These findings indicate a possible selective role for PAD-isozymes in hypoxia response and tolerance

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

This work was supported by the National Institute of General Medical Sciences [GM131919].In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.PostprintPeer reviewe