Biology subjects

Thirumlaikumar, V. P.

Publications and source records attributed to Thirumlaikumar, V. P..

4 recordsLinked to original sources

bioRxiv2026

Thiol depletion and disruption of proteostasis contribute to the phytotoxicity of juglone

O_LIJuglone is the phytotoxic 1,4-naphthoquinone responsible for the allelopathic effects of black walnut (Juglans nigra), yet how plants perceive and respond to juglone remain poorly understood. C_LIO_LIWe conducted transcriptome profiling of rosettes and roots of Arabidopsis thaliana exposed to juglone from 30 min to 5 d, along with targeted metabolic profiling, biochemical assays, and untargeted proteomics to gain a systems-level understanding of how plants respond to juglone and to test hypotheses underlying its phytotoxicity. C_LIO_LIJuglone exposure induced expression of genes involved in glutathione, cysteine, and sulfur metabolism pathways, and in protein homeostasis. We found that juglone depletes the pool of reduced glutathione (GSH) in roots, in part, through conjugation. We demonstrate that via upregulation of transcription factors (NAC53 and NAC78), the response to juglone activates components of the proteasome stress regulon and triggers extensive proteome remodeling with engagement of the autophagy pathway when proteasome capacity is limited. C_LIO_LIOur findings (i) indicate that thiol depletion and disruption of proteostasis through juglones dual redox cycling and alkylation activities are central to its phytotoxicity, (ii) cast doubt on previous reports that juglone targets a specific enzyme in plants or other organisms, and (iii) provide insight into how the chemical properties of allelopathic quinones shape their ecological roles. C_LI

plant biology↗

bioRxiv2024

Small molecule oxybutynin rescues proliferative capacity of complex III-defective MPCs

Mitochondrial disease encompasses a group of genetically inherited disorders hallmarked by an inability of the respiratory chain to produce sufficient ATP. These disorders present with multisystemic pathologies that predominantly impact highly energetic tissues such as skeletal muscle. There is no cure or effective treatment for mitochondrial disease. We have discovered a small molecule known as oxybutynin that can bypass Complex III mitochondrial dysfunction in primary murine and human skeletal muscle progenitor cells (MPCs). Oxybutynin administration improves MPC proliferative capacity, enhances cellular glycolytic function, and improves myotube formation. Mechanistically, results from our isothermal shift assay indicates that oxybutynin interacts with a suite of proteins involved in mRNA processing which then trigger the upregulation biological pathways to circumvent CIII mitochondrial dysfunction. Taken together, we provide evidence for the small molecule oxybutynin as a potential therapeutic candidate for the future treatment of CIII mitochondrial dysfunction.

cell biology↗

bioRxiv2024

Identification of cell-type-specific response to silicon treatment in soybean leaves through single nucleus RNA-sequencing

In agriculture, mineral nutrients uptake and deposition profoundly influence plant development, stress resilience, and productivity. Despite its classification as a non-essential element, silicon (Si) is crucial in plant physiology, particularly in defense response and stress mitigation. While genetic and molecular mechanisms of Si uptake and transport are well-studied in monocots, particularly rice, its role in dicot species, such as soybean, remains unclear at the cellular and molecular levels. Traditional bulk transcriptomics methods lack the resolution to uncover cellular heterogeneity. Here, we present a study by utilizing single-nucleus RNA sequencing (snRNA-seq) to dissect cellular responses to Si accumulation in soybean leaves. Our analysis revealed distinct cellular populations, including a novel Si-induced cell cluster within vascular cells, suggesting a specific mechanism of Si distribution. Si treatment induced the expression of defense-related genes, particularly enriched in vascular cells, highlighting their specialized role in activating plant defense mechanisms. Moreover, Si modulated the expression of genes involved in RNA silencing, phytoalexin biosynthesis, and immune receptor signaling, suggesting a mechanism of transcriptional priming of genes involved in defense responses. We further investigated putative Si transporters, revealing differential expression patterns in response to Si treatment, suggesting presence of active and gradient-based transport mechanisms. Our findings shed light on the vital biotic stress regulatory networks governed by Si treatment in soybean leaves, paving potential strategies for enhancing stress tolerance and agronomic performance in crops.

plant biology↗

bioRxiv2024

Mapping protein-metabolite interactions in E. coli by integrating chromatographic techniques and co-fractionation mass spectrometry.

In our pursuit of understanding the protein-metabolite interactome, we introduced PROMIS, a co-fractionation mass spectrometry (CF-MS) technique focusing on biosynthetic and regulatory processes. However, the challenge lies in distinguishing true interactors from coincidental co-elution when a metabolite co-fractionates with numerous proteins. To address this, we integrated two chromatographic techniques-- size exclusion and ion exchange--to enhance the mapping of protein-metabolite interactions (PMIs) in Escherichia coli. This integration aims to refine the PMI network by considering size and charge characteristics, resulting in 994 interactions involving 51 metabolites and 465 proteins. The PMI network is enriched for known and predicted interactions validating our approachs efficacy. Furthermore, the analysis of protein targets for different metabolites revealed novel functional insights, such as the connection between proteinogenic dipeptides and fatty acid biosynthesis. Notably, we uncovered an inhibitory interaction between the riboflavin degradation product lumichrome and orotate phosphoribosyltransferase (PyrE), a key enzyme in de novo pyrimidine synthesis. Lumichrome supplementation mimicked the biofilm formation inhibition observed in a{Delta} pyrE mutant strain, suggesting lumichrome role in integrating pyrimidine and riboflavin metabolism with quorum sensing and biofilm formation. In summary, our integrated chromatographic approach significantly advances PMI mapping, offering novel insights into functional associations and potential regulatory mechanisms in E. coli.

biochemistry↗