@article {9105, title = {Macrophage metabolic reprogramming during dietary stress influences adult body size in Drosophila [Central Imaging and Flow Cytometry Facility (INT)]}, journal = {EMBO Rep}, year = {2025}, month = {2025 Sep 09}, abstract = {

Immune cells are increasingly recognized as nutrient sensors; however, their developmental role in regulating growth under homeostasis or dietary stress remains elusive. Here, we show that Drosophila larval macrophages, in response to excessive dietary sugar (HSD), reprogram their metabolic state by activating glycolysis, thereby enhancing TCA-cycle flux, and increasing lipogenesis-while concurrently maintaining a lipolytic state. Although this immune-metabolic configuration correlates with growth retardation under HSD, our genetic analyses reveal that enhanced lipogenesis supports growth, whereas glycolysis and lipolysis are growth-inhibitory. Notably, promoting immune-driven lipogenesis offsets early growth inhibition in imaginal discs caused by glycolytic and lipolytic immune-metabolic states. Our findings reveal a model of immune-metabolic imbalance, where growth-suppressive states (glycolysis, lipolysis) dominate over a growth-supportive lipogenic state, thereby impairing early organ size control and ultimately affecting adult size. Overall, this study provides important insights into dietary stress-induced immune-metabolic reprogramming and its link to organ size regulation and early developmental plasticity.

}, issn = {1469-3178}, doi = {10.1038/s44319-025-00574-7}, author = {Mahanta, Anusree and Najar, Sajad Ahmad and Hariharan, Nivedita and Bhowmick, Ajit and Rizvi, Syed Iqra and Goyal, Manisha and Parupalli, Preethi and Subramanian, Ramaswamy and Giangrande, Angela and Palakodeti, Dasaradhi and Mukherjee, Tina} } @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 = {

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.

}, 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 {4869, title = {Dual control of dopamine in Drosophila myeloid-like progenitor cell proliferation and regulation of lymph gland growth. [Central Imaging \& Flow Cytometry Facility]}, journal = {EMBO Rep}, year = {2022}, month = {2022 Apr 27}, pages = {e52951}, type = {Journal Article}, abstract = {

In Drosophila, definitive haematopoiesis takes place in a specialized organ termed "lymph gland". It harbours multi-potent stem-like blood progenitor cells whose development controls overall growth of this haematopoietic tissue and formation of mature blood cells. With respect to its development, neurotransmitters have emerged as potent regulators of blood-progenitor cell development and function. In this study, we extend our understanding of neurotransmitters and show that progenitors are self-sufficient with regard to synthesizing dopamine, a well-established neurotransmitter. These cells also have modules for dopamine sensing through the receptor and transporter. We found that modulating expression of these components in progenitor cells affected lymph gland growth, which suggested growth-promoting function of dopamine in blood-progenitor cells. Cell-cycle analysis of developing lymph glands revealed an unexpected requirement for intracellular dopamine in moderating the progression of early progenitor cells from S to G2 phase of the cell cycle, while activation of dopamine receptor signalling later in development regulated their progression from G2 and entry into mitosis. The dual capacity in which dopamine operated, first intracellularly to coordinate S/G2 transition and later extracellularly in G2/M transition, was critical for the growth of the lymph gland. Overall, the data presented highlight a novel non-canonical use of dopamine in the myeloid system that reveals an uncharacterized function of intracellular dopamine in cell-cycle phasing with outcomes on haematopoietic growth and immunity as well.

}, keywords = {cell cycle, dopamine signalling, dopamine synthesis, haematopoietic progenitors, proliferation}, issn = {1469-3178}, doi = {10.15252/embr.202152951}, url = {embopress.org/doi/abs/10.15252/embr.202152951}, author = {Kapoor, Ankita and Padmavathi, Achalla and Madhwal, Sukanya and Mukherjee, Tina} } @article {1637, title = {Metabolic control of cellular immune-competency by odors in Drosophila [Mass Spectrometry - Metabolomics Facility (INT)]}, journal = {Elife}, volume = {9}, year = {2020}, month = {2020 Dec 29}, abstract = {

Studies in different animal model systems have revealed the impact of odors on immune cells; however, any understanding on why and how odors control cellular immunity remained unclear. We find that employ an olfactory-immune cross-talk to tune a specific cell type, the lamellocytes, from hematopoietic-progenitor cells. We show that neuronally released GABA derived upon olfactory stimulation is utilized by blood-progenitor cells as a metabolite and through its catabolism, these cells stabilize Sima/HIFα protein. Sima capacitates blood-progenitor cells with the ability to initiate lamellocyte differentiation. This systemic axis becomes relevant for larvae dwelling in wasp-infested environments where chances of infection are high. By co-opting the olfactory route, the preconditioned animals elevate their systemic GABA levels leading to the upregulation of blood-progenitor cell Sima expression. This elevates their immune-potential and primes them to respond rapidly when infected with parasitic wasps. The present work highlights the importance of the olfaction in immunity and shows how odor detection during animal development is utilized to establish a long-range axis in the control of blood-progenitor competency and immune-priming.

}, issn = {2050-084X}, doi = {10.7554/eLife.60376}, author = {Madhwal, Sukanya and Shin, Mingyu and Kapoor, Ankita and Goyal, Manisha and Joshi, Manish K and Ur Rehman, Pirzada Mujeeb and Gor, Kavan and Shim, Jiwon and Mukherjee, Tina} }