@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 {536,
	title = {Does reversible cysteine oxidation link the Western diet to cardiac dysfunction?},
	journal = {FASEB J},
	volume = {28},
	year = {2014},
	month = {2014 May},
	pages = {1975-87},
	abstract = {<p>Using a novel cysteine thiol labeling strategy coupled with mass spectrometric analysis, we identified and quantified the changes in global reversible cysteine oxidation of proteins in the left ventricle of hearts from mice with metabolic syndrome-associated diastolic dysfunction. This phenotype was induced by feeding a high-fat, high-sucrose, type-2 diabetogenic diet to C57BL/6J mice for 8 mo. The extent of reversible thiol oxidation in relationship to the total available (free and reducible) level of each cysteine could be confidently determined for 173 proteins, of which 98 contained cysteines differentially modified >=1.5-fold by the diet. Our findings suggest that the metabolic syndrome leads to potentially deleterious changes in the oxidative modification of metabolically active proteins. These alterations may adversely regulate energy substrate flux through glycolysis, β-oxidation, citric acid (TCA) cycle, and oxidative phosphorylation (oxphos), thereby contributing to maladaptive tissue remodeling that is associated with, and possibly contributing to, diastolic left ventricular dysfunction.</p>
},
	keywords = {Animals, Chromatography, Liquid, Citric Acid Cycle, Cysteine, Diet, Fatty Acids, Glycolysis, Heart Diseases, Male, Mice, Mice, Inbred C57BL, Myocardial Contraction, Myocardium, Obesity, Oxidative Phosphorylation, Oxygen, Phenotype, Protein Processing, Post-Translational, Proteomics, Reactive Nitrogen Species, Reactive Oxygen Species, Sulfhydryl Compounds, Tandem Mass Spectrometry},
	issn = {1530-6860},
	doi = {10.1096/fj.13-233445},
	author = {Behring, Jessica B and Kumar, Vikas and Whelan, Stephen A and Chauhan, Pratibha and Siwik, Deborah A and Costello, Catherine E and Colucci, Wilson S and Cohen, Richard A and McComb, Mark E and Bachschmid, Markus M}
}
