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; Tina L Tootle

doi:10.64898/2026.01.06.697938

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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

PMID: 41542428

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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

Details

Title: Subtitle: ATGL-mediated lipid droplet lipolysis promotes collective migration in Drosophila
Creators: Israel J Wipf - University of Iowa
Emma J Lowden - University of Iowa
Julia R Dorale - Department of Biology, University of Iowa, Iowa City, IA 52242
Kennedy F Godfredsen - University of Iowa
Michelle S Giedt - University of Iowa
Tina L Tootle - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.64898/2026.01.06.697938
PMID: 41542428
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Number of pages: 63 pages
Grant note: T32 GM144636 / NIGMS NIH HHS P40 OD018537 / NIH HHS R35 GM144057 / NIGMS NIH HHS
Language: English
Date posted: 01/07/2026
Academic Unit: Anatomy and Cell Biology; Biology
Record Identifier: 9985129655702771

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