Biology subjects

Manna, M.

Publications and source records attributed to Manna, M..

4 recordsLinked to original sources

bioRxiv2026

Corilagin attenuates high glucose-induced neurotoxicity and mitochondrial dysfunction through restoration of the AMPK-SIRT1-PGC1α-TFAM signaling axis

Mitochondrial dysfunction and oxidative stress represent two interconnected, primary causes for Diabetic Neuropathy (DN); however, the majority of currently available anti-diabetic therapies have focused on glucose control as opposed to neurodegenerative downstream effects. Corilagin, is an ellagitannin having high anti-oxidant properties; however, it has not been evaluated against hyperglycemia induced neuronal injury. The present study demonstrates the ability of Corilagin to protect against mitochondrial dysfunction via models of diabetic nephropathy and cerebral ischemia. High glucose (50 mM, 24 hr) was utilized to induce diabetes like conditions in the SH-SY5Y human neuroblastoma Cell Line. High glucose induced significant decreases in cell viability, increases in intracellular and mitochondrial reactive oxygen species, depletion of reduced glutathione reserves, induces apoptosis, and causes mitochondrial depolarization and fragmentation. Corilagin pre-treatment attenuated each of these high-glucose induced effects by protecting against mitochondrial membrane potential loss and maintaining mitochondrial network morphology while reducing apoptotic cell fraction relative to glucose alone. Additionally, these protective effects were accompanied by restoration of AMPK phosphorylation and up-regulation of SIRT1, PGC1 and TFAM, components that are part of the principal signaling pathway that regulates mitochondrial biogenesis; therefore, therefore, this pathway may contribute mechanistically to the cyto-protective effect of Corilagin. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/740444v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1be4a92org.highwire.dtl.DTLVardef@11d6e9org.highwire.dtl.DTLVardef@1346757org.highwire.dtl.DTLVardef@16c9f1e_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Proposed mechanism underlying the neuroprotective effects of Corilagin against high glucose-induced mitochondrial dysfunction.High glucose suppresses AMPK phosphorylation, leading to downregulation of the SIRT1-PGC-1-TFAM signaling axis, increased intracellular and mitochondrial reactive oxygen species (ROS), glutathione depletion, apoptosis, mitochondrial depolarization, and mitochondrial fragmentation. Corilagin pretreatment restores AMPK activation and the downstream SIRT1-PGC-1-TFAM pathway, thereby reducing oxidative stress, preserving intracellular glutathione, preventing apoptosis, maintaining mitochondrial membrane potential, and protecting mitochondrial network integrity. C_FIG

cell biology↗

bioRxiv2025

A positive feedback loop of MPK3-PIN1A trafficking-auxin flux trio governs dual gravitropic and wounding response in rice

The auxin flow in plants plays a pivotal role in gravitropic organ movement and tissue regeneration following injury. However, the regulatory aspects of these phenomena are not entirely understood. In this study, we found that hyperactivity of MAP Kinase 3 (MPK3) led to downregulation of PINs and reduction in tissue auxin content, impairing gravitropic response of rice and accelerating tissue senescence following mechanical wounding. The MPK3 was found to phosphorylate PIN1A majorly at its Ser351 residue, mutation of which into its phospho-mimic variant enhanced latters endosomal trafficking and consequently improved auxin flux. Further, overexpression of the phospho-null variant of PIN1A lowered gravitropic response of rice, thus causing wider tiller angle similar to the pin1a knockout lines. Additionally, upon wounding, their tissue senescence was faster in comparison to the overexpression lines of wild-type and phospho-mimic variants of PIN1A, which also displayed improved resistance to wounding by Bipolaris oryzae. The PIN1A trafficking-mediated auxin flux also regulated MPK3 activity via a positive feedback loop. Together, these results uncover a novel feedback loop encompassing "MPK3-PIN1A trafficking-auxin flux" trio that regulates dual gravitropic and wounding response in rice.

plant biology↗

bioRxiv2024

Kingdom-specific lipid unsaturation shapes up sequence evolution in membrane arm subunits of eukaryotic respiratory complexes

Sequence evolution of protein complexes (PCs) is constrained by protein-protein interactions (PPIs). PPI-interfaces are predominantly conserved and hotspots for disease-related mutations. How lipid-protein interactions (LPIs) constrain sequence evolution of membrane- PCs? We explore Respiratory Complexes (RCs) as a case study as these allow to compare sequence evolution in subunits exposed to both lipid-rich inner-mitochondrial membrane (IMM) and aqueous matrix. We find that lipid-exposed surfaces of the IMM-subunits but not of the matrix subunits are populated with non-PPI disease-causing mutations signifying LPIs in stabilizing RCs. Further, IMM-subunits including their exposed surfaces show high intra- kingdom sequence conservation but remarkably diverge beyond. Molecular Dynamics simulation suggests contrasting LPIs of structurally superimposable but sequence-wise diverged IMM-exposed helices of Complex I (CI) subunit Ndufa1 from human and Arabidopsis depending on kingdom-specific unsaturation of cardiolipin fatty acyl chains. in cellulo assays consolidate inter-kingdom incompatibility of Ndufa1-helices due to the lipid- exposed amino acids. Plant-specific unsaturated fatty acids in human cells also trigger CI- instability. Taken together, we posit that altered LPIs calibrate sequence evolution at the IMM-arms of eukaryotic RCs.

cell biology↗

bioRxiv2022

Phase transition in atomistic simulations of model membrane with thylakoid lipids of red algae

Marine algae are diverse photosynthetic organisms, profoundly rich in bioactive compounds. Temperature is a major factor in algal cultivation and biomass production. At the cellular level, the change of temperature is reflected in oscillating algal lipid/fatty acid profile and inhibition of photosynthetic activities. The function of thylakoid membrane system is intimately dependent on its lipid matrix, however the molecular organization of these lipid membranes and particularly their adaptive arrangements under temperature stress remain largely unexplored. The present work employing extensive atomistic simulations provides the first atomistic view of the phase transition and domain coexistence in model membrane composed of thylakoid lipids of a marine alga, between 10-40 {degrees}C. The model membrane undergoes a transition from a gel-like phase at 10-15 {degrees}C to a homogeneous liquid-disordered phase at 40 {degrees}C. Clear evidences of spontaneous phase separation into coexisting nanoscale domains are detected at intermediate temperatures. Particularly at 25-30 {degrees}C, we identified the formation of a stable rippled phase, where the gel-like domains rich in saturated and nearly hexagonally packed lipids separated from fluid-like domains enriched in lipids containing polyunsaturated chains. Cholesterol impairs the phase transition and the emergence of domains, and induces a fairly uniform liquid-ordered phase in the membrane over the temperatures studied. The results have implications in understanding the role of lipids in temperature adaptation in algal.

biophysics↗