Biology subjects

Jose, G. P.

Publications and source records attributed to Jose, G. P..

4 recordsLinked to original sources

bioRxiv2026

Ether lipid remodeling during neuronal differentiation prevents ferroptosis

Ferroptosis is a form of cell death driven by iron-dependent lipid peroxidation, with specific lipid species playing key roles in modulating susceptibility. Among these, ether lipids have shown conflicting effects, being linked to both protection and sensitization. Here, we dissect the relationship between lipid structure and ferroptosis sensitivity and explain how ether lipids exert context-dependent effects. Ether lipids can promote ferroptosis through a metabolic bias towards the accumulation of polyunsaturated acyl chains and ethanolamine head groups, whereas this pro-ferroptotic tendency is counterbalanced by the anti-ferroptotic vinyl ether moiety introduced by plasmanylethanolamine desaturase 1. We show that this protective effect is critical for preventing ferroptosis in hiPSC-derived neurons, which accumulate otherwise pro-ferroptotic ether lipids during differentiation. This effect is not solely due to its antioxidant properties but also stems from the reprogramming of mitochondrial respiration. The lack of vinyl ether bonds leads to multiple mitochondrial defects, including increased mitochondrial reactive oxygen species (ROS), lower membrane potential, and abnormal cristae structures. These findings indicate that vinyl ether bonds in ether lipids offer dual ferroptosis resistance by scavenging ROS and minimizing its production at the mitochondrial level. The disruption of this system in Caenorhabditis elegans leads to iron-induced death and impaired motility. Thus, our study reveals ether lipid structural remodeling as a key regulator of ferroptosis sensitivity in neurons.

cell biology↗

bioRxiv2024

Differentiating the mechanism of antibacterial activities of nano and ionic copper by using Escherichia coli as a model microorganism

In this study, the effect of polymer stabilized copper nanoparticles and ionic copper on the growth, nucleic acid pool, reactive oxygen species generation, cell surface lipopolysaccharide, outer membrane protein profile and cell surface morphology of Escherichia coli were investigated. Copper nanoparticles exhibited a superior bactericidal activity associated with increased nucleic acid degradation, reactive oxygen species generation and change in the outer membrane protein profile compared to ionic copper in a concentration dependent manner. Although, there was no change in the outer membrane lipopolysaccharide profile, inductively coupled plasma mass spectrometry analysis of nano- and ionic copper treated Escherichia coli cells revealed that more amounts of copper nanoparticles were transported inside the cells compared to the ionic counterpart up to 500 M concentrations. Interestingly, copper nanoparticles at 1000 M concentration could induce membrane pit formation whereas ionic copper failed to exhibit such property under the same experimental conditions. Based on these observations it can be concluded that both nano- and ionic copper exert their antibacterial action through the generation of reactive oxygen species, degradation of cellular nucleic acids and alteration of membrane protein profile, but with a significant difference in the effective concentration range due to the differential cellular transport.

microbiology↗

bioRxiv2024

Acyltransferases in the first step of glycerophospholipid synthesis have redundant and non-redundant roles in sn-1 acyl chain regulation, ether lipid levels, and cell survival

The increased use of lipidomics analyses in biomedical research made it crucial to understand correctly how lipid compositions are regulated. Lipid acyl chains are important regulators of membrane physicochemical properties, and are incorporated by various acyltransferases. The acyltransferases implicated in the first step of glycerophospholipid synthesis, the GPATs and GNPAT, have distinct localizations and substrate preferences. This suggests that they have distinct roles on lipid regulation, but a complete understanding of their redundant and non-redundant functions is missing. We report here a comprehensive analysis of cells having mutations in GPATs and GNPAT, either alone or in combinations. Our results suggest that the balance between GPATs and GNPAT affect the levels of ether lipids, together with glycerophospholipid acyl chain length and unsaturation. In addition, we found that lipid synthesis initiated at peroxisomes, but not mitochondria, is sufficient to provide the lipid synthesis flux required for normal cell growth. Our study unveils the multifaceted roles of the first step of de novo glycerophospholipid synthesis, thus leading to a better understanding of how lipidomes are shaped.

cell biology↗

bioRxiv2022

A metabolic labeling-based chemoproteomic platform unravels the physiological roles of choline metabolites

Choline is an essential nutrient for mammalian cells. Our understanding of the cellular functions of choline and its metabolites, independent of their roles as choline lipid metabolism intermediates, remains limited. In addition to fundamental cellular physiology, this knowledge has implications for cancer biology because elevated choline metabolite levels are a hallmark of cancer. Here, we establish the mammalian choline metabolite-interacting proteome by utilizing a photocrosslinkable choline probe. To design this probe, we performed metabolic labeling experiments with structurally diverse choline analogs that resulted in the serendipitous discovery of a choline lipid headgroup remodeling mechanism involving sequential dealkylation and methylation steps. We demonstrate that phosphocholine inhibits the binding of one of the proteins identified, the attractive anticancer target, p32, to its endogenous ligands and to the promising p32-targeting anticancer agent, Lyp-1. Our results reveal that choline metabolites play vital roles in cellular physiology by serving as modulators of protein function.

biochemistry↗