Oligogalacturonides Enhance Resistance against Aphids through Pattern-Triggered Immunity and Activation of Salicylic Acid Signaling

The remarkable capacity of the generalist aphid Myzus persicae to resist most classes of pesticides, along with the environmental and human health risks associated with these agrochemicals, has necessitated the development of safer and greener solutions to control this agricultural pest. Oligogalacturonides (OGs) are pectin-derived molecules that can be isolated from fruit industry waste. OGs have been shown to efficiently stimulate plant defenses against pathogens such as Pseudomonas syringae and Botrytis cinerea. However, whether OGs confer resistance against phytophagous insects such as aphids remains unknown. Here, we treated Arabidopsis plants with OGs and recorded their effects on the feeding performance and population of M. persicae aphids. We also identified the defense mechanism triggered by OGs in plants through the analysis of gene expression and histological approaches. We found that OG treatments increased their resistance to M. persicae infestation by reducing the offspring number and feeding performance. Furthermore, this enhanced resistance was related to a substantial accumulation of callose and reactive oxygen species and activation of the salicylic acid signaling pathway.     

Dual Mode of Mitochondrial ROS Action during Reprogramming to Pluripotency

Essential changes in cell metabolism and redox signaling occur during the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). In this paper, using genetic and pharmacological approaches, we have investigated the role of electron transport chain (ETC) complex-I (CI) of mitochondria in the process of cell reprogramming to pluripotency. Knockdown of NADH-ubiquinone oxidoreductase core subunits S1 (Ndufs1) or subunit B10 (Ndufb10) of the CI or inhibition of this complex with rotenone during mouse embryonic fibroblast (MEF) reprogramming resulted in a significantly decreased number of induced pluripotent stem cells (iPSCs). We have found that mitochondria and ROS levels due course of the reprogramming tightly correlate with each other, both reaching peak by day 3 and significantly declining by day 10 of the process. The transient augmentation of mitochondrial reactive oxygen species (ROS) could be attenuated by antioxidant treatment, which ameliorated overall reprogramming. However, ROS scavenging after day 3 or during the entire course of reprogramming was suppressive for iPSC formation. The ROS scavenging within the CI-deficient iPSC-precursors did not improve, but further suppressed the reprogramming. Our data therefore point to distinct modes of mitochondrial ROS action during the early versus mid and late stages of reprogramming. The data further substantiate the paradigm that balanced levels of oxidative phosphorylation have to be maintained on the route to pluripotency.     

Molecular Mechanisms of Nitric Oxide (NO) Signaling and Reactive Oxygen Species (ROS) Homeostasis during Abiotic Stresses in Plants

Abiotic stressors, such as drought, heavy metals, and high salinity, are causing huge crop losses worldwide. These abiotic stressors are expected to become more extreme, less predictable, and more widespread in the near future. With the rapidly growing human population and changing global climate conditions, it is critical to prevent global crop losses to meet the increasing demand for food and other crop products. The reactive gaseous signaling molecule nitric oxide (NO) is involved in numerous plant developmental processes as well as plant responses to various abiotic stresses through its interactions with various molecules. Together, these interactions lead to the homeostasis of reactive oxygen species (ROS), proline and glutathione biosynthesis, post-translational modifications such as S-nitrosylation, and modulation of gene and protein expression. Exogenous application of various NO donors positively mitigates the negative effects of various abiotic stressors. In view of the multidimensional role of this signaling molecule, research over the past decade has investigated its potential in alleviating the deleterious effects of various abiotic stressors, particularly in ROS homeostasis. In this review, we highlight the recent molecular and physiological advances that provide insights into the functional role of NO in mediating various abiotic stress responses in plants.     

Linking Reactive Oxygen Species (ROS) to Abiotic and Biotic Feedbacks in Plant Microbiomes: The Dose Makes the Poison

In nature, plants develop in complex, adaptive environments. Plants must therefore respond efficiently to environmental stressors to maintain homeostasis and enhance their fitness. Although many coordinated processes remain integral for achieving homeostasis and driving plant development, reactive oxygen species (ROS) function as critical, fast-acting orchestrators that link abiotic and biotic responses to plant homeostasis and development. In addition to the suite of enzymatic and non-enzymatic ROS processing pathways that plants possess, they also rely on their microbiota to buffer and maintain the oxidative window needed to balance anabolic and catabolic processes. Strong evidence has been communicated recently that links ROS regulation to the aggregated function(s) of commensal microbiota and plant-growth-promoting microbes. To date, many reports have put forth insightful syntheses that either detail ROS regulation across plant development (independent of plant microbiota) or examine abiotic–biotic feedbacks in plant microbiomes (independent of clear emphases on ROS regulation). Here we provide a novel synthesis that incorporates recent findings regarding ROS and plant development in the context of both microbiota regulation and plant-associated microbes. Specifically, we discuss various roles of ROS across plant development to strengthen the links between plant microbiome functioning and ROS regulation for both basic and applied research aims.     

MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines

In cancer therapy, radioresistance or chemoresistance cells are major problems. We established clinically relevant radioresistant (CRR) cells that can survive over 30 days after 2 Gy/day X-ray exposures. These cells also show resistance to anticancer agents and hydrogen peroxide (H₂O₂). We have previously demonstrated that all the CRR cells examined had up-regulated miR-7-5p and after miR-7-5p knockdown, they lost radioresistance. However, the mechanism of losing radioresistance remains to be elucidated. Therefore, we investigated the role of miR-7-5p in radioresistance by knockdown of miR-7-5p using CRR cells. As a result, knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe²⁺ amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount. H₂O₂ treatment after ALOX12 overexpression led to the enhancement of intracellular H₂O₂ amount and lipid peroxidation. By contrast, miR-7-5p knockdown seemed not to be involved in COX-2 and glycolysis signaling but affected the morphology of CRR cells. These results indicate that miR-7-5p control radioresistance via ROS generation that leads to ferroptosis.     

Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells

In the treatment of breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukemia (CML) using BCR-ABL inhibitors, the appearance of a gatekeeper mutation (T315I) in BCR-ABL is a serious issue. Therefore, the development of novel drugs that overcome acquired resistance to BCR-ABL inhibitors by CML cells is required. We previously demonstrated that a bis-pyridinium fullerene derivative (BPF) induced apoptosis in human chronic myeloid leukemia (CML)-derived K562 cells partially through the generation of reactive oxygen species (ROS). We herein show that BPF enhanced the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase (MEK-ERK) pathway in a ROS-independent manner. BPF-induced apoptosis was attenuated by trametinib, suggesting the functional involvement of the MEK-ERK pathway in apoptosis in K562 cells. In addition, the constitutive activation of the MEK-ERK pathway by the enforced expression of the BRAFV600E mutant significantly increased the sensitivity of K562 cells to BPF. These results confirmed for the first time that BPF induces apoptosis in K562 cells through dual pathways—ROS production and the activation of the MEK-ERK pathway. Furthermore, BPF induced cell death in transformed Ba/F3 cells expressing not only BCR-ABL but also T315I mutant through the activation of the MEK-ERK pathway. These results indicate that BPF is as an effective CML drug that overcomes resistance to BCR-ABL inhibitors.     

The BAG2 and BAG6 Genes Are Involved in Multiple Abiotic Stress Tolerances in Arabidopsis Thaliana

The BAG proteins are a family of multi-functional co-chaperones. In plants, BAG proteins were found to play roles both in abiotic and biotic stress tolerance. However, the function of Arabidopsis BAG2 remains largely unknown, whereas BAG6 is required for plants’ defense to pathogens, although it remains unknown whether BAG6 is involved in plants’ tolerance to abiotic stresses. Here, we show that both BAG2 and BAG6 are expressed in various tissues and are upregulated by salt, mannitol, and heat treatments and by stress-related hormones including ABA, ethylene, and SA. Germination of bag2, bag6 and bag2 bag6 seeds is less sensitive to ABA compared to the wild type (WT), whereas BAG2 and BAG6 overexpression lines are hypersensitive to ABA. bag2, bag6, and bag2 bag6 plants show higher survival rates than WT in drought treatment but display lower survival rates in heat-stress treatment. Consistently, these mutants showed differential expression of several stress- and ABA-related genes such as RD29A, RD29B, NCED3 and ABI4 compared to the WT. Furthermore, these mutants exhibit lower levels of ROS after drought and ABA treatment but higher ROS accumulation after heat treatment than the WT. These results suggest that BAG2 and BAG6 are negatively involved in drought stress but play a positive role in heat stress in Arabidopsis.     

Mitochondrial Transfer in Cancer: A Comprehensive Review

Depending on their tissue of origin, genetic and epigenetic marks and microenvironmental influences, cancer cells cover a broad range of metabolic activities that fluctuate over time and space. At the core of most metabolic pathways, mitochondria are essential organelles that participate in energy and biomass production, act as metabolic sensors, control cancer cell death, and initiate signaling pathways related to cancer cell migration, invasion, metastasis and resistance to treatments. While some mitochondrial modifications provide aggressive advantages to cancer cells, others are detrimental. This comprehensive review summarizes the current knowledge about mitochondrial transfers that can occur between cancer and nonmalignant cells. Among different mechanisms comprising gap junctions and cell-cell fusion, tunneling nanotubes are increasingly recognized as a main intercellular platform for unidirectional and bidirectional mitochondrial exchanges. Understanding their structure and functionality is an important task expected to generate new anticancer approaches aimed at interfering with gains of functions (e.g., cancer cell proliferation, migration, invasion, metastasis and chemoresistance) or damaged mitochondria elimination associated with mitochondrial transfer.     

Mitogen-Activated Protein (MAP) Kinases in Plant Metal Stress: Regulation and Responses in Comparison to Other Biotic and Abiotic Stresses

Exposure of plants to toxic concentrations of metals leads to disruption of the cellular redox status followed by an accumulation of reactive oxygen species (ROS). ROS, like hydrogen peroxide, can act as signaling molecules in the cell and induce signaling via mitogen-activated protein kinase (MAPK) cascades. MAPK cascades are evolutionary conserved signal transduction modules, able to convert extracellular signals to appropriate cellular responses. In this review, our current understanding about MAPK signaling in plant metal stress is discussed. However, this knowledge is scarce compared to research into the role of MAPK signaling in the case of other abiotic and biotic stresses. ROS production is a common response induced by different stresses and undiscovered analogies may exist with metal stress. Therefore, further attention is given to MAPK signaling in other biotic and abiotic stresses and its interplay with other signaling pathways to create a framework in which the involvement of MAPK signaling in metal stress may be studied.