Biology subjects

Bondarenko, O.

Publications and source records attributed to Bondarenko, O..

4 recordsLinked to original sources

bioRxiv2025

SnRK1.1 Coordinates Organ-Specific Growth-Defense Programs via Transcriptomic Rewiring in Arabidopsis thaliana

SnRK1 (Sucrose non-fermenting-1-Related Kinase 1) is a master regulator of cellular energy homeostasis in plants, coordinating developmental and metabolic responses under environmental and internal stress conditions. Here, we demonstrate that its catalytic subunit, KIN10, orchestrates organ-specific growth-defense programs in Arabidopsis thaliana through transcriptomic rewiring. Using RNA-seq profiling, we reveal that kin10 knockout mutants exhibit extensive transcriptional reprogramming in roots, particularly in pathways linked to signal perception, cell wall remodeling, and intracellular trafficking, which correlates with impaired root growth and reduced root hair elongation upon Pseudomonas syringae infection. In contrast, KIN10 overexpression (KIN10-OE) lines display constitutive defense activation in shoots, including elevated expression of genes associated with reactive oxygen species (ROS) production and salicylic acid (SA) signaling, leading to enhanced ROS accumulation and growth trade-offs. kin10 roots show muted responses to biotic stimuli, while KIN10-OE shoots prioritize defense over growth. These findings position KIN10 as a critical integrator of energy status and immune signaling, enabling fine-tuned, tissue-specific responses essential for optimizing plant adaptation to dynamic environmental challenges.

plant biology↗

bioRxiv2021

Small-molecule inhibitors of the RNA m6A demethylase FTO potently support the survival of dopamine neurons

The fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, is an important regulator of central nervous system development, neuronal signalling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. In FTO binding and activity-inhibition assays the two best inhibitors demonstrated Kd = 185 nM; IC50 = 1.46 M (compound 2) and Kd = 337 nM; IC50 = 28.9 M (compound 3). Importantly, the treatment of mouse midbrain dopamine neurons with the compounds promoted cellular survival and rescued them from growth factor deprivation induced apoptosis already at nanomolar concentrations. Moreover, these inhibitors demonstrated good blood-brain-barrier penetration in the model system, 31.7% and 30.8%, respectively. The compounds 2 and 3 protected dopamine neurons with greater potency than our recently developed alkylation repair homolog protein 5 (AlkBH5) m6A demethylase inhibitors. Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Further refinement of the lead compounds identified in this study, can also lead to unprecedented breakthroughs in the treatment of neurodegenerative diseases.

neuroscience↗

bioRxiv2019

Non-enzymatically oxidized arachidonic acid regulates mouse spermatogenic cell T-type Ca2+ currents

During spermatogenesis, phospholipids and fatty acids (FAs) play an important role both as structural components of spermatogenic cell plasma membranes and as molecular messengers that trigger the differentiation of the male germ cell line. However, spontaneous oxidation of plasma membrane phospholipids and FAs causes a decrease in mammalian fertility. In the present report, we examine the effects of non-enzymatically oxidized arachidonic acid (AAox) on mouse spermatogenic T-type Ca2+ currents (ICaT) due to their physiological relevance during spermatogenesis. AAox effects on the biophysical parameters of ICaT were significantly different from those previously reported for AA. AAox left shifted the I-V curve peak and both activation and steady-state inactivation curves. ICaT deactivation kinetics were slower in presence of AAox and the time for its recovery from inactivation increased significantly. Therefore, the fraction of inactivated Ca2+ channels of spermatogenic cells is increased at voltages where they are usually active. The inhibition of ICaT by AAox could contribute to the infertility phenotype and to the observed apoptotic state of spermatogenic cells induced by oxidized FAs.

physiology↗

bioRxiv2018

Bacterial plasma membrane is the main cellular target of silver nanoparticles in Escherichia coli and Pseudomonas aeruginosa

Silver nanoparticles (AgNP) are widely used in consumer products, mostly due to their excellent antimicrobial properties. One of the well-established antibacterial mechanisms of AgNP is their efficient contact with bacteria and dissolution on cell membranes. To our knowledge, the primary mechanism of cell wall damage and the event(s) initiating bactericidal action of AgNP are not yet elucidated.\n\nIn this study we used a combination of different assays to reveal the effect of AgNP on i) bacterial envelope in general, ii) outer membrane (OM) and iii) on plasma membrane (PM). We showed that bacterial PM was the main target of AgNP in Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. AgNP depolarized bacterial PM, induced the leakage of the intracellular K+, inhibited respiration and caused the depletion of the intracellular ATP. In contrast, AgNP had no significant effect on the bacterial OM. Most of the adverse effects on bacterial envelope and PM occurred within the seconds and in the concentration range of 7-160 M AgNP, depending on the bacteria and assay used, while irreversible inhibition of bacterial growth (minimal bactericidal concentration after 1-h exposure of bacteria to AgNP) occurred at 40 M AgNP for P. aeruginosa and at 320 M AgNP for E. coli.\n\nFlow cytometry analysis showed that AgNP were binding to P. aeruginosa but not to E. coli cells and were found inside the P. aeruginosa cells. Taking into account that AgNP did not damage OM, we speculate that AgNP entered P. aeruginosa via specific mechanism, e.g., transport through porins.

microbiology↗