Disruption of mTORC2 via Rictor Knockdown Alters Fat Storage and Survival in Drosophila

High-sugar diets are a major driver of metabolic disease and reduced lifespan across species¹, yet the genetic mechanisms linking dietary excess to aging are not completely underwood.² The mechanistic target of rapamycin complex 2 (mTORC2), defined by its scaffolding subunit Rictor, is a conserved nutrient-sensing kinase complex that phosphorylates downstream AGC family kinases including Akt, SGK1, and PKCα to regulate cell survival, metabolic homeostasis, and stress resistance.² Despite its established importance, mTORC2 remains far less characterized than mTORC1, and its specific contributions to lifespan and fat metabolism under dietary stress are not well defined. Using Drosophila melanogaster as a genetic model system, this study examines how loss of Rictor function affects survival and body composition under regular and high-sugar dietary conditions. Experiments were conducted across four experimental groups: yellow-white (YW) controls and Rictor^Δ2 loss-of-function mutants, each maintained on either a regular or high-sugar diet. We found that Rictor mutants exhibit dramatically reduced lifespan relative to YW controls under both dietary conditions, confirming that mTORC2 signaling is required for normal survival. In terms of body composition, Rictor mutants on a regular diet showed significantly elevated TAG levels compared to YW controls, but HS diet normalized this difference by elevating TAG in YW flies to levels comparable to Rictor mutants. Finally, we found that the healthspan of Rictor mutants was dramatically reduced across dietary conditions. Together, these findings suggest that mTORC2 loss impairs lipid mobilization rather than simply promoting lipid synthesis, and that energy substrate availability, rather than total fat accumulation, may be the primary determinant of survival outcomes in this model. Additionally, mTORC2 is crucial to healthy aging and function in old age. Further work is needed to dissect the biochemical and tissue-specific mechanisms underlying these phenotypes.