Speaker: Peiduo Liu, graduate candidate in the Bai Lab

Title: “Metabolic regulation of lipid homeostasis in Drosophila melanogaster"

Abstract: Lipid metabolism is critical for physiological homeostasis, yet its tissue-specific regulation remains elusive. Using Drosophila melanogaster as a genetic model, we elucidate organ-specific lipid-mediated pathways in cardiac protection, renal lipid homeostasis, and hepatic stress responses. We demonstrate that mTORC2 promotes Drp1-mediated mitochondrial fission to protect the Drosophila heart from high-fat diet (HFD)-induced contractile dysfunction. Heart-specific rictor, the key subunit of mTORC2, knockdown impairs fission and exacerbates cardiac defects. Additionally, we establish that the Malpighian tubules (MTs), analogous to mammalian renal tubules, are the primary site of plasmalogen biosynthesis in Drosophila. Knockdown of Kua, the enzyme for the last step of the plasmalogen biosynthesis, in MTs reduces circulating plasmalogen levels and impairs cardiac function, highlighting the inter-organ lipid dynamics. Furthermore, we uncover a phenylalanine-dependent mechanism regulating dFOXO nuclear localization in larval oenocytes, modulating starvation-induced steatosis. These findings provide insights into tissue-specific lipid regulation and offer a foundation for exploring metabolic stress responses across organisms.