RT Journal Article
SR Electronic
T1 Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.02.454724
DO 10.1101/2021.08.02.454724
A1 Michelle S. Giedt
A1 Jonathon M. Thomalla
A1 Matthew R. Johnson
A1 Zon Weng Lai
A1 Tina L. Tootle
A1 Michael A. Welte
YR 2022
UL http://biorxiv.org/content/early/2022/03/17/2021.08.02.454724.abstract
AB A key factor controlling oocyte quality and fertility is lipids. Even though lipid droplets (LDs) are crucial regulators of lipid metabolism, their roles in fertility are poorly understood. During Drosophila oogenesis, LD accumulation in nurse cells coincides with dynamic actin remodeling necessary for late-stage follicle morphogenesis and fertility. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when Pxt, the enzyme responsible for prostaglandin (PG) synthesis, is missing. Dominant genetic interactions and PG treatment of follicles in vitro reveal that ATGL and Pxt act in the same pathway to regulate actin remodeling, with ATGL upstream of Pxt. Further, lipidomic analysis detects arachidonic acid (AA) containing triglycerides in ovaries. Because AA is the substrate for Pxt, we propose that ATGL releases AA from LDs to drive PG synthesis necessary for follicle development. We also find that exogenous AA is toxic to follicles in vitro, and LDs modulate this toxicity. This leads to the model that LDs both sequester AA to limit toxicity, and release AA via ATGL to drive PG production. We speculate that the same pathways are conserved across organisms to regulate oocyte development and promote fertility.Competing Interest StatementThe authors have declared no competing interest.