Wipf, I. J. | bioRxiv Science

bioRxiv2026

ATGL-mediated lipid droplet lipolysis promotes collective migration in Drosophila

While lipid droplets (LDs), dynamic organelles central to lipid and energy homeostasis, are implicated in cancer cell migration, their roles during collective cell migration remain unknown. We use Drosophila border cell migration as an in vivo model of invasive, collective cell migration to dissect the roles of LDs and the conserved LD lipase, Adipose Triglyceride Lipase (ATGL). Border cell LDs undergo dynamic changes and decrease in volume by the end of migration. Loss of ATGL increases LD volume, whereas border cell overexpression depletes LDs. Loss, border cell knockdown or overexpression of ATGL delays migration and blocks delamination. Further, loss of ATGL disrupts border cell mitochondria - it alters morphology, reduces membrane potential and increases reactive oxygen species. These results demonstrate that tight regulation of lipid mobilization from LDs, including for energy production, drives delamination and collective migration. Our findings not only have the potential to inform how cancer cells exploit LDs to promote their invasive behaviors but also highlight the crucial role of LDs in migration during development, hinting at their broader significance in diverse migratory contexts.

cell biology↗

bioRxiv2025

The lipid droplet protein Jabba promotes actin remodeling downstream of prostaglandin signaling during Drosophila oogenesis

Growing evidence supports that lipid droplets (LDs) are critical for producing high-quality oocytes. However, the functions of LDs during oocyte development remain largely unknown. Using Drosophila oogenesis as a model, we previously discovered the LD-associated Adipose Triglyceride Lipase (ATGL) promotes actin remodeling necessary for oocyte development by providing the substrate for producing lipid signals termed prostaglandins (PGs). Here we find that Jabba, a LD-associated protein best known for its role in anchoring other proteins to LDs, also promotes PG-dependent actin remodeling. Overexpression of Jabba results in thickened cortical actin and excessive actin bundles, whereas loss of Jabba results in cortical actin breakdown and severely defective actin bundle formation. We find that Jabba regulates actin remodeling independently of ATGL but in conjunction with PG signaling. These data support that there are two PG signaling pathways that promote actin remodeling: one PG pathway that is dependent on ATGL and the other requires Jabba. Overexpression of Jabba rescues the actin defects when PG signaling is lost. Together these data lead to the model that PGs produced independently of ATGL positively regulate Jabba to promote actin remodeling necessary for follicle morphogenesis and the production of a fertilization competent oocyte. Significance statementO_LIAcross organisms, lipid droplets accumulate during oocyte development and are implicated in fertility. The functions of lipid droplets during oogenesis are poorly understood. C_LIO_LIThe authors use the genetic tools and well-characterized process of Drosophila oogenesis to reveal that Jabba, a lipid droplet anchoring protein, is a new downstream effector of prostaglandin signaling and promotes actin remodeling necessary for producing a fertilization competent oocyte. C_LIO_LIThe results extend prior studies connecting lipid droplet proteins, prostaglandins, and actin remodeling, providing insight into how these critical conserved factors contribute to high-quality oocytes. C_LI

cell biology↗