Biology subjects

Dogra, V.

Publications and source records attributed to Dogra, V..

5 recordsLinked to original sources

bioRxiv2025

Oxidative stress-induced proteolytic activation of polyphenol oxidase triggers an oxidized flavonoids-mediated stress signaling in Camellia sinensis

Environmental perturbations often increase reactive oxygen species (ROS) production, inducing oxidative damage to various biomolecules. The cellular system utilizes ROS or ROS-generated metabolites to instigate signaling pathways, resulting in acclimation, growth inhibition, or programmed cell death (PCD) for sustaining stress. Various stress-generated or stress-activated signaling components and downstream pathways are identified in model plants; however, they are largely unexplored in non-model plants. Here, we report a stress-induced proteolytic activation of an evolutionarily conserved chloroplast-localized enzyme, polyphenol oxidase (PPO), that oxidizes catechins into theaflavins (TFs) and initiates a stress signaling under drought in Camellia sinensis (Tea). Germplasm-based analysis revealed a heightened proteolytic activation of PPO and consequent TFs accumulation in drought-susceptible genotypes. Transcriptome analysis revealed that PPO activation and TFs accumulation were linked to the activation of UPR(unfolded protein response)-like response, which was reinforced by virus-induced silencing and overexpression of PPO, and direct feeding of TFs in tea plants. Pharmacological treatments revealed that TFs interact with HSP90, activating a canonical IRE-bZIP60-dependent ER stress pathway resulting in PCD. Similar proteolytic activation of PPO and subsequent instigation of stress signaling in other plant species (tomato and wheat) demonstrated that PPO acts as an evolutionarily conserved stress sensor, instigating an inter-organelle communication in plants. Significance statementPPO, an evolutionarily conserved and chloroplast/plastid localized enzyme, senses stress and undergoes proteolytic activation to generate oxidized flavonoids/quinones that function as signaling molecules in Tea and likely in other plants. The oxidized flavonoids modulate protein folding machinery and augment folding stress, especially in the ER, inducing canonical IRE1-bZI60-dependent PCD. The finding shows that specific secondary metabolites likely have roles in instigating intra- and intercellular communication to sustain the adversities of stress in different plant species.

plant biology↗

bioRxiv2023

Network Pharmacology and molecular docking approach to unveil the mechanism of Hypericum perforatum in the management of Alzheimer's disorder

The pathogenesis of Alzheimers disease (AD) is not fully understood which limits the availability of safer and more efficient therapeutic strategies for the management of AD. There has been growing interest in recent years in exploring the potential of herbal medicines as a source of safer and alternative therapeutic strategies for the management of AD. This study aims to discover the mechanism of Hypericum perforatum in the management of AD using network pharmacology and molecular docking approach. The results of network pharmacology suggest that 39 bioactive molecules of H. perforatum target 127 genes associated with AD, amongst which ATP-dependent translocase, acetylcholinesterase, amyloid-{beta} precursor protein, {beta}-secretase 1, carbonic anhydrase 2, dipeptidyl peptidase 4, epidermal growth factor receptor, tyrosine-protein phosphatase non-receptor type 1, -synuclein, and vascular endothelial growth factor A seems to be the prominent target of these molecules. Further, the results of molecular docking predicted amentoflavone, I3,II8-biapigenin, rutin, miquelianin, quercetin, luteolin, and nicotiflorin as a promising modulator of target proteins which were determined from network pharmacology to be associated with AD. Our findings suggest that H. perforatum could be a safer and more promising alternative therapeutic strategy for the management of AD by targeting multiple pathways of AD pathogenesis.

pharmacology and toxicology↗

bioRxiv2023

Characterization of Tryptophan Oxidation Affecting D1 Degradation by FtsH in the Photosystem II Quality Control of Chloroplasts

Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH. Competing Interest StatementThe authors have no conflict of interest, financial or otherwise, in relation to this study Impact StatementOxidative modification of Tryptophan residues in the reaction center protein D1 may be a key to drive the Photosystem II repair, likely enhancing accessibility of FtsH protease to D1.

plant biology↗

bioRxiv2021

TIC236 gain-of-function mutations unveil the link between plastid division and plastid protein import

The chloroplast translocons TOC75 and TIC236 are homologs of the bacterial translocation and assembly module (Tam) A and TamB involved in protein export. Here, we unveil a TIC236-allied component, the chloroplast outer membrane protein CRUMPLED LEAF (CRL), absence of which impairs plastid division and induces autoimmune responses in Arabidopsis thaliana. A forward genetic screen aimed at finding crl suppressors revealed multiple TIC236 gain-of-function mutations (TIC236GFs). Despite the low sequence identity between TIC236 and bacterial TamB, each mutated TIC236GF residue is conserved in TamB. Consistently, a tic236- knockdown mutant exhibited multiple lesion phenotypes similar to crl, indicating a shared functionality of CRL and TIC236. Ensuing reverse genetic analyses revealed genetic interaction between CRL and SP1, a RING-type ubiquitin E3 ligase, as well as with the plastid protease FTSH11, which function in TOC and TIC protein turnover, respectively. Loss of either SP1 or FTSH11 rescued crl mutant phenotypes to varying degrees due to increased translocon levels. Consistent with impaired plastid division exhibited by both crl and tic236-knockdown mutants, CRL interacts with the transit peptides of proteins essential in plastid division, and TIC236GF mutant proteins reinforce their import via increased TIC236 stability. Overall, our data shed new light on the links between plastid division, plant stress response and plastid protein import. We have also isolated and characterized the first GF mutants exhibiting increased protein import efficiency, which may inspire chloroplast engineering for agricultural advancement.

plant biology↗

bioRxiv2019

A novel pathway linking plasma membrane and chloroplasts is co-opted by pathogens to suppress salicylic acid-dependent defences

Chloroplasts are crucial players in the activation of defensive hormonal responses during plant-pathogen interactions. Here, we show that a plant virus-encoded protein re-localizes from the plasma membrane to chloroplasts upon triggering plant defence, interfering with the chloroplast-dependent activation of anti-viral salicylic acid (SA) biosynthesis. Strikingly, we have found that plant pathogens from different kingdoms seem to have convergently evolved to target chloroplasts and impair SA-dependent defences following an association with membranes, which is based on the co-existence of two subcellular targeting signals, an N-myristoylation site and a chloroplast transit peptide. This pattern is also present in plant proteins, at least one of which conversely activates SA defences from the chloroplast. Taken together, our results suggest that a pathway linking plasma membrane to chloroplasts and activating defence exists in plants, and that such pathway has been co-opted by plant pathogens during host-pathogen co-evolution to promote virulence through suppression of SA responses.

plant biology↗