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ATGL-mediated lipid droplet lipolysis promotes collective migration in Drosophila
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ATGL-mediated lipid droplet lipolysis promotes collective migration in Drosophila

Israel J Wipf, Emma J Lowden, Julia R Dorale, Kennedy F Godfredsen, Michelle S Giedt and Tina L Tootle
bioRxiv
Cold Spring Harbor Laboratory
01/07/2026
DOI: 10.64898/2026.01.06.697938
PMCID: PMC12803247
PMID: 41542428
url
https://doi.org/10.64898/2026.01.06.697938View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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 border cell migration as an 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.
Migration delamination border cells lipid droplets lipolysis Drosophila

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