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Ferroptosis is a non-apoptotic form of cell death that can be triggered by small molecules or conditions that inhibit glutathione biosynthesis or the glutathione-dependent antioxidant enzyme glutathione peroxidase 4 (GPX4). This lethal process is defined by the iron-dependent accumulation of lipid reactive oxygen species and depletion of plasma membrane polyunsaturated fatty acids. Cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression may be sensitized to this process. Conversely, a number of small molecule inhibitors of ferroptosis have been identified, including ferrostatin-1 and liproxstatin-1, which can block pathological cell death events in brain, kidney and other tissues. Recent work has identified a number of genes required for ferroptosis, including those involved in lipid and amino acid metabolism. Outstanding questions include the relationship between ferroptosis and other forms of cell death, and whether activation or inhibition of ferroptosis can be exploited to achieve desirable therapeutic ends.

CoMoO.sub.4 materials were prepared through a simple hydrothermal method and developed as highly efficient peroxidase mimics for colorimetric determination of H.sub.2O.sub.2. Based on the different experimental conditions in the synthesis process, the CoMoO.sub.4 materials present distinct morphologies, structures, surface properties, and peroxidase mimetic activities. Among them, CoMoO.sub.4 nanobelts (NBs) display the best intrinsic peroxidase mimetic abilities due to the high-energy (100) facet exposed, more Co active sites at (100) facet, more negative potential, and larger specific surface area. It can efficiently catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H.sub.2O.sub.2 to generate a blue oxide. In view of the excellent peroxidase mimetic catalytic activity of CoMoO.sub.4 NBs, a rapid, convenient, and ultrasensitive method was successfully established for the visual and colorimetric determination of H.sub.2O.sub.2. The method exhibits good selectivity, practicability, stability, and reusability, and has a detection limit of 0.27 [mu]M. The peroxidase mimetic catalytic mechanism of CoMoO.sub.4 NBs was illustrated according to the kinetic and active species trapping experiments. The method has a good potential for rapid and sensitive determination of H.sub.2O.sub.2 for biomedical analysis.

Ferroptosis is a non-apoptotic form of cell death induced by small molecules in specific tumour types, and in engineered cells overexpressing oncogenic RAS. Yet, its relevance in non-transformed cells and tissues is unexplored and remains enigmatic. Here, we provide direct genetic evidence that the knockout of glutathione peroxidase 4 ( Gpx4 ) causes cell death in a pathologically relevant form of ferroptosis. Using inducible Gpx4 −/− mice, we elucidate an essential role for the glutathione/Gpx4 axis in preventing lipid-oxidation-induced acute renal failure and associated death. We furthermore systematically evaluated a library of small molecules for possible ferroptosis inhibitors, leading to the discovery of a potent spiroquinoxalinamine derivative called Liproxstatin-1, which is able to suppress ferroptosis in cells, in Gpx4 −/− mice, and in a pre-clinical model of ischaemia/reperfusion-induced hepatic damage. In sum, we demonstrate that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection. Ferroptosis is a form of non-apoptotic cell death with unclear physiological relevance. Conrad and colleagues now report that unrestrained ferroptosis can lead to renal failure. They also identify a small molecule that limits ferroptosis in vivo .

Class III peroxidases are secretory enzymes which belong to a ubiquitous multigene family in higher plants and have been identified to play role in a broad range of physiological and developmental processes. Potentially, it is involved in generation and detoxification of hydrogen peroxide (H 2 O 2 ), and their subcellular localization reflects through three different cycles, namely peroxidative cycle, oxidative and hydroxylic cycles to maintain the ROS level inside the cell. Being an antioxidant, class III peroxidases are an important initial defence adapted by plants to cope with biotic and abiotic stresses. Both these stresses have become a major concern in the field of agriculture due to their devastating effect on plant growth and development. Despite numerous studies on plant defence against both the stresses, only a handful role of class III peroxidases have been uncovered by its functional characterization. This review will cover our current understanding on class III peroxidases and the signalling involved in their regulation under both types of stresses. The review will give a view of class III peroxidases and highlights their indispensable role under stress conditions. Its future application will be discussed to showcase their importance in crop improvement by genetic manipulation and by transcriptome analysis.

Nanozymes are nanomaterials with enzyme-like catalytic properties. They are attractive reagents because they do not have the same limitations of natural enzymes (e.g., high cost, low stability and difficult storage). To test, optimize and compare nanozymes, it is important to establish fundamental principles and systematic standards to fully characterize their catalytic performance. Our 2018 protocol describes how to characterize the catalytic activity and kinetics of peroxidase nanozymes, the most widely used type of nanozyme. This approach was based on Michaelis–Menten enzyme kinetics and is now updated to take into account the unique physicochemical properties of nanomaterials that determine the catalytic kinetics of nanozymes. The updated procedure describes how to determine the number of active sites as well as other physicochemical properties such as surface area, shape and size. It also outlines how to calculate the hydroxyl adsorption energy from the crystal structure using the density functional theory method. The calculations now incorporate these measurements and computations to better characterize the catalytic kinetics of peroxidase nanozymes that have different shapes, sizes and compositions. This updated protocol better describes the catalytic performance of nanozymes and benefits the development of nanozyme research since further nanozyme development requires precise control of activity by engineering the electronic, geometric structure and atomic configuration of the catalytic sites of nanozymes. The characterization of the catalytic activity of peroxidase nanozymes and the evaluation of their kinetics can be performed in 4 h. The procedure is suitable for users with expertise in nano- and materials technology. Key points Nanozymes are nanoparticles designed to have catalytic properties similar to those of natural enzymes. Design and optimization of nanozyme properties require analytical methods to characterize their physical properties as well as their catalytic activity and kinetics. This is an updated protocol for measuring catalytic behavior that incorporates data from measured physical properties unique to each nanoparticle as well as density functional theory calculations into the Michaelis–Menten approach. Developing optimal nanozymes requires standardized methods for measuring their catalytic activity and reaction kinetics. This protocol integrates enzyme based Michaelis–Menten kinetics with measured physical properties and computational methods.

Single phase metastable [alpha]-AgVO.sub.3 microrods with high crystallinity, tetragonal rod-like microstructure, uniform particle size distribution, and good dispersion were synthesized by direct coprecipitation at room temperature. They are shown to be viable peroxidase mimics that catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H.sub.2O.sub.2. Kinetic analysis indicated typical Michaelis-Menten catalytic behavior. The findings were used to design a colorimetric assay for H.sub.2O.sub.2, best measured at 652 nm. The method has a linear response in the 60 to 200 [mu]M H.sub.2O.sub.2 concentration range, with a 2 [mu]M detection limit. Benefitting from the chemical stability of the microrods, the method is well reproducible. It also is easily performed and highly specific.

It is well established that ferroptosis is primarily controlled by glutathione peroxidase 4 (GPX4). Surprisingly, we observed that p53 activation modulates ferroptotic responses without apparent effects on GPX4 function. Instead, ALOX12 inactivation diminishes p53-mediated ferroptosis induced by reactive oxygen species stress and abrogates p53-dependent inhibition of tumour growth in xenograft models, suggesting that ALOX12 is critical for p53-mediated ferroptosis. The ALOX12 gene resides on human chromosome 17p13.1, a hotspot of monoallelic deletion in human cancers. Loss of one Alox12 allele is sufficient to accelerate tumorigenesis in Eμ-Myc lymphoma models. Moreover, ALOX12 missense mutations from human cancers abrogate its ability to oxygenate polyunsaturated fatty acids and to induce p53-mediated ferroptosis. Notably, ALOX12 is dispensable for ferroptosis induced by erastin or GPX4 inhibitors; conversely, ACSL4 is required for ferroptosis upon GPX4 inhibition but dispensable for p53-mediated ferroptosis. Thus, our study identifies an ALOX12-mediated, ACSL4-independent ferroptosis pathway that is critical for p53-dependent tumour suppression. Chu et al. identify the lipoxygenase ALOX12 as essential for p53-dependent ferroptosis in a pathway independent of GPX4. Monoallelic deletion of Alox12 abrogates p53-mediated suppression in a model of Eµ-Myc -driven lymphoma.

Heme-containing peroxidases secreted by fungi are a fascinating group of biocatalysts with various ecological and biotechnological implications. For example, they are involved in the biodegradation of lignocelluloses and lignins and participate in the bioconversion of other diverse recalcitrant compounds as well as in the natural turnover of humic substances and organohalogens. The current review focuses on the most recently discovered and novel types of heme-dependent peroxidases, aromatic peroxygenases (APOs), and dye-decolorizing peroxidases (DyPs), which catalyze remarkable reactions such as peroxide-driven oxygen transfer and cleavage of anthraquinone derivatives, respectively, and represent own separate peroxidase superfamilies. Furthermore, several aspects of the “classic” fungal heme-containing peroxidases, i.e., lignin, manganese, and versatile peroxidases (LiP, MnP, and VP), phenol-oxidizing peroxidases as well as chloroperoxidase (CPO), are discussed against the background of recent scientific developments.

Root Hairs (RHs) growth is influenced by endogenous and by external environmental signals that coordinately regulate its final cell size. We have recently determined that RH growth was unexpectedly boosted when Arabidopsis thaliana seedlings are cultivated at low temperatures. It was proposed that RH growth plasticity in response to low temperature was linked to a reduced nutrient availability in the media. Here, we explore the molecular basis of this RH growth response by using a Genome Wide Association Study (GWAS) approach using Arabidopsis thaliana natural accessions. We identify the poorly characterized PEROXIDASE 62 (PRX62) and a related protein PRX69 as key proteins under moderate low temperature stress. Strikingly, a cell wall protein extensin (EXT) reporter reveals the effect of peroxidase activity on EXT cell wall association at 10 °C in the RH apical zone. Collectively, our results indicate that PRX62, and to a lesser extent PRX69, are key apoplastic PRXs that modulate ROS-homeostasis and cell wall EXT-insolubilization linked to RH elongation at low temperature. Arabidopsis root hair growth is enhanced at low temperatures. Here the authors show that the class III peroxidases PRX62 and PRX69 modulate ROS homeostasis and cell wall characteristics, and promote root hair elongation at low temperature.

This work provides spectroscopic, catalytic, and stability fingerprints of two new bacterial dye-decolorizing peroxidases (DyPs) from Bacillus subtilis (BsDyP) and Pseudomonas putida MET94 (PpDyP). DyPs are a family of microbial heme-containing peroxidases with wide substrate specificity, including high redox potential aromatic compounds such as synthetic dyes or phenolic and nonphenolic lignin units. The genes encoding BsDyP and PpDyP, belonging to subfamilies A and B, respectively, were cloned and heterologously expressed in Escherichia coli. The recombinant PpDyP is a 120-kDa homotetramer while BsDyP enzyme consists of a single 48-kDa monomer. The optimal pH of both enzymes is in the acidic range (pH 4–5). BsDyP has a bell-shape profile with optimum between 20 and 30 °C whereas PpDyP shows a peculiar flat and broad (10–30 °C) temperature profile. Anthraquinonic or azo dyes, phenolics, methoxylated aromatics, and also manganese and ferrous ions are substrates used by the enzymes. In general, PpDyP exhibits higher activities and accepts a wider scope of substrates than BsDyP; the spectroscopic data suggest distinct heme microenvironments in the two enzymes that might account for the distinctive catalytic behavior. However, the Bs enzyme with activity lasting for up to 53 h at 40 °C is more stable towards temperature or chemical denaturation than the PpDyP. The results of this work will guide future optimization of the biocatalytis towards their utilization in the fields of environmental or industrial biotechnology.