676C Poster - 10. Cell biology: Cytoskeleton, organelles and trafficking
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Kazuki Ueda ¹; Matthew Anderson-Baron ^1,2; Nathan Hoeven ³; Julie Haskins ¹; Andrew Simmonds ¹

Affiliations:
1) Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7; 2) Future Fields Ltd. Edmonton, AB, Canada T5H 0L5; 3) Ross Shepard High School, Edmonton, AB, Canada T5M 2P2

Keywords:
n. peroxisomomes; m. CNS

A systemic lipid homeostasis is crucial for proper functioning and development of organ systems. Peroxisome is a membrane-bound organelle and is one of the central hubs of lipid metabolism. A congenital, autosomal recessive disorders affecting one of 14 core peroxisome genes, Peroxins (Pex), leads to a spectrum of peroxisome biogenesis disorders (PBDs) exhibiting neurological deficits and developmental delays in children currently with palliative treatments as only available options.
Peroxisomes are thought to associate and coordinate with lipid droplets (LDs) (cellular fat stores) to regulate β-oxidation of fatty acids and promote synthesis of plasmalogens and docohexanoic acids. Our lab has recently identified peroxisome-independent functions of two Pex proteins (or Peroxins), Pex13 and Pex14, in promoting lipid storage at LDs in Drosophila melanogaster. In particular, we observed that Pex14 prevented localization of hormone sensitive lipase (Hsl), but not brummer (adipose triglyceride lipase homologue), to the surface of the LDs when co-overexpressed in Drosophila S2 cells under a condition that induces lipolysis.
The Drosophila larval fat body (human adipose tissue and liver equivalent) stores lipids in large LDs and releases them during later development or during starvation conditions. We employed various Pex mutant and fat body-specific Pex knockdown (Pex FKD) flies to examine roles Peroxins have in lipid storage in vivo. When wild-type (WT) and Pex FKD (Pex1, Pex13, and Pex14) were fed on holidic food (low fat), they remained relatively stable and exhibited similar survival rates. When raised on holidic+lard food (high fat), the survival rates of both WT and Pex1 FKD larvae remained similar to the previous feeding condition while Pex13 and Pex14 FKD displayed a reduction in their survival rates suggesting lipotoxic effects due to an abnormal increase in systemic lipid levels. Compared to the WT larvae, Pex13, Pex14, and Pex16 FKD showed reduced brain size while Pex11 and Pex19 did not seem to be affected. Compared to the WT larvae, only Pex13 and Pex14 mutants displayed reduced fat storage in the fat body indicated by reductions in size and quantity of LDs while Pex1 and Pex5 mutants seemed to display increased fat storage. Intriguingly, the dsRNA-mediated KD of Pex16 in S2 cells dramatically reduced Pex14 mRNA expression suggesting co-regulation of the two Pex genes. Overall, the evidence seems to support the unique roles of both Pex13 and Pex14 in promoting lipid storage in the fat body of Drosophila melanogaster. Moreover, these roles are independent of peroxisomes as other Pex FKD and mutants that also similarly affect peroxisome functions were seemingly unaffected.