Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila

Abstract

SummaryStem cells reside in specialized microenvironments known as niches. During Drosophila development, glial cells provide a niche that sustains the proliferation of neural stem cells (neuroblasts) during starvation. We now find that the glial cell niche also preserves neuroblast proliferation under conditions of hypoxia and oxidative stress. Lipid droplets that form in niche glia during oxidative stress limit the levels of reactive oxygen species (ROS) and inhibit the oxidation of polyunsaturated fatty acids (PUFAs). These droplets protect glia and also neuroblasts from peroxidation chain reactions that can damage many types of macromolecules. The underlying antioxidant mechanism involves diverting PUFAs, including diet-derived linoleic acid, away from membranes to the core of lipid droplets, where they are less vulnerable to peroxidation. This study reveals an antioxidant role for lipid droplets that could be relevant in many different biological contexts.

The why, when and how of lipid droplet diversity

“…In terms of the variability of lipid droplet number in cells of a given population, it has been proposed that the lipid droplets of some cells act as 'sponges' by absorbing excess fatty acids that have been esterified into TAGs . Such a protective mechanism potentially also explains the accumulation of lipid droplets in glial cells during oxidative stress (Bailey et al, 2015;Liu et al, 2015). A protection from lipotoxicity could also explain the existence of small lipid droplets, which are prone to disappearing, in cells that also include growing lipid droplets .…”

“…However, the specialized function of certain cell types is reflected by the lipid composition of their lipid droplets. Examples include the enrichment of stellate cell lipid droplets with retinyl esters (D'Ambrosio et al, 2011) and of foamy monocyte lipid droplets with the uncommon fatty acid cis-7-hexadecanoic acid (Guijas et al, 2016), as well as the accumulation of polyunsaturated fatty acids -such as linoleic acid in larval (Bailey et al, 2015) and peroxidated lipids -in glia cells of adult Drosophila (Liu et al, 2015). In terms of the lipid-dropletassociated proteins, a core set of about 50 proteins has been found to decorate lipid droplets in various cellular systems (reviewed in Hodges and Wu, 2010).…”

Androgen control of lipid metabolism in prostate cancer: novel insights and future applications

“…Fatty acids that are synthesized or acquired by prostate cancer cells undergo catabolism via beta-oxidation for energy production (Carracedo et al 2013), are stored in lipid droplets to protect them from harmful peroxidation (Bailey et al 2015, Liu et al 2015, or are ultimately converted to more complex phospholipids that are key components of cellular membranes (Fig. 1).…”

Metabolism meets development at Wiston House

“…In the brain, glia are important for sustaining neuronal function and they also provide a niche that regulates the proliferation of NSCs. Working with Drosophila, the Gould laboratory discovered that in response to hypoxia or oxidative stress, glia divert polyunsaturated fatty acids away from membranes to the core of lipid droplets, which function as anti-oxidant organelles limiting the peroxidation chain reactions that would otherwise damage neuroblasts (Bailey et al, 2015). One could envisage a similar mechanism also being used by tumor cells that encounter significant oxidative stress.…”