@article {9118,
	title = {Metabolic coupling of ROS generation and antioxidant synthesis by the GABA shunt pathway in myeloid-like blood progenitor cells of Drosophila. [CIFF \& Metabolomics Facility]},
	journal = {PLoS Genet},
	volume = {21},
	year = {2025},
	month = {2025 Sep},
	pages = {e1011602},
	abstract = {<p>Redox balance is crucial for normal development of stem and progenitor cells that reside in oxidative environments. In this study, we explore the mechanisms of redox homeostasis in such niches and show that myeloid-like blood progenitor cells of the Drosophila larval lymph gland, that generate reactive oxygen species (ROS), moderate it developmentally by de novo synthesizing glutathione (GSH) to ensure redox balance. During lymph gland development, as the blood-progenitor cells oxidize pyruvate via the TCA cycle leading to the generation of ROS, GABA-shunt restricts pyruvate dehydrogenase (PDH) activity and consequently TCA cycle flux. This moderation enables a metabolic rerouting of TCA-derived oxaloacetate (OAA) to pyruvate via gluconeogenesis, which is necessary to sustain serine levels, the rate-limiting precursor for de novo GSH synthesis. Disruption of GABA metabolism causes metabolic imbalance, marked by excessive PDH activity and heightened TCA cycle flux. This results in reduced OAA availability, impaired gluconeogenic capacity, and insufficient serine/GSH production, ultimately leading to ROS dysregulation. Overall, this study identifies a unique metabolic framework in blood progenitor cells, where the GABA shunt, by restraining PDH and TCA cycle activity, maintains ROS at developmental levels. By coupling TCA-derived metabolites to GSH production, this state enables the TCA cycle to support both ROS generation and ROS scavenging, ensuring the developmental roles of ROS while preserving progenitor homeostasis.</p>
},
	keywords = {Animals, Antioxidants, Citric Acid Cycle, Drosophila, Drosophila melanogaster, Drosophila Proteins, gamma-Aminobutyric Acid, Gluconeogenesis, Glutathione, Hematopoietic Stem Cells, Larva, Myeloid Cells, Oxidation-Reduction, Oxidative Stress, Pyruvic Acid, Reactive Oxygen Species},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1011602},
	author = {Goyal, Manisha and Tiwari, Sakshi and Arora, Jagriti and Cooper, Bruce and Subramanian, Ramaswamy and Mukherjee, Tina}
}
@article {513,
	title = {L-Plastin S-glutathionylation promotes reduced binding to β-actin and affects neutrophil functions. (Mass Spectrometry)},
	journal = {Free Radic Biol Med},
	volume = {86},
	year = {2015},
	month = {2015 Sep},
	pages = {1-15},
	abstract = {<p>Posttranslational modifications (PTMs) of cytoskeleton proteins due to oxidative stress associated with several pathological conditions often lead to alterations in cell function. The current study evaluates the effect of nitric oxide (DETA-NO)-induced oxidative stress-related S-glutathionylation of cytoskeleton proteins in human PMNs. By using in vitro and genetic approaches, we showed that S-glutathionylation of L-plastin (LPL) and β-actin promotes reduced chemotaxis, polarization, bactericidal activity, and phagocytosis. We identified Cys-206, Cys-283, and Cys-460as S-thiolated residues in the β-actin-binding domain of LPL, where cys-460 had the maximum score. Site-directed mutagenesis of LPL Cys-460 further confirmed the role in the redox regulation of LPL. S-Thiolation diminished binding as well as the bundling activity of LPL. The presence of S-thiolated LPL was detected in neutrophils from both diabetic patients and db/db mice with impaired PMN functions. Thus, enhanced nitroxidative stress may results in LPL S-glutathionylation leading to impaired chemotaxis, polarization, and bactericidal activity of human PMNs, providing a mechanistic basis for their impaired functions in diabetes mellitus.</p>
},
	keywords = {Actins, Adult, Amino Acid Sequence, Animals, Case-Control Studies, Cell Polarity, Chemotaxis, Diabetes Mellitus, Female, Glutathione, HEK293 Cells, Humans, Male, Mice, Inbred C57BL, Mice, Obese, Microfilament Proteins, Middle Aged, Molecular Sequence Data, Neutrophils, Nitric Oxide, Oxidative Stress, Protein Binding, Protein Processing, Post-Translational, Young Adult},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2015.04.008},
	author = {Dubey, Megha and Singh, Abhishek K and Awasthi, Deepika and Nagarkoti, Sheela and Kumar, Sachin and Ali, Wahid and Chandra, Tulika and Kumar, Vikas and Barthwal, Manoj K and Jagavelu, Kumaravelu and S{\'a}nchez-G{\'o}mez, Francisco J and Lamas, Santiago and Dikshit, Madhu}
}
