Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila.
Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila.
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DOI：
10.1016/j.cell.2015.09.020
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发表时间：
2015-10-08
期刊：
影响因子：
64.5
通讯作者：
Gould AP
中科院分区：
文献类型：
--
作者：
Bailey AP;Koster G;Guillermier C;Hirst EM;MacRae JI;Lechene CP;Postle AD;Gould AP
干细胞存在于特殊的微环境中，这种微环境被称为小生境。在果蝇的发育过程中，胶质细胞提供了一个支持饥饿期间神经干细胞(神经母细胞)增殖的利基。我们现在发现，在低氧和氧化应激条件下，神经胶质细胞的壁龛也能保持神经母细胞的增殖。在氧化应激过程中，在壁龛胶质细胞中形成的脂滴限制了活性氧物种(ROS)的水平，并抑制了多不饱和脂肪酸(PUFAs)的氧化。这些液滴保护胶质细胞和神经母细胞免受过氧化连锁反应的影响，过氧化连锁反应可能会损害许多类型的大分子。潜在的抗氧化机制涉及将多不饱和脂肪酸，包括饮食衍生的亚油酸，从膜转移到脂滴的核心，在那里它们不太容易被过氧化。这项研究揭示了脂滴的抗氧化作用，这可能与许多不同的生物背景有关。氧化应激刺激神经干细胞壁龛中脂滴的生物合成脂滴保护壁龛和神经干细胞免受多不饱和脂肪酸过氧化的伤害多不饱和脂肪酸在脂滴中比细胞膜中更不容易被过氧化氧化，脂滴可以作为抗氧化器官保护果蝇神经干细胞免受缺氧触发的ROS的影响。它们将多不饱和脂肪酸从质膜中隔离出来，从而保护这些脂质免受有害的过氧化，否则会危及细胞的增殖。
Stem 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. Oxidative stress stimulates lipid droplet biosynthesis in a neural stem cell niche Lipid droplets protect niche and neural stem cells from damaging PUFA peroxidation PUFAs are less vulnerable to peroxidation in lipid droplets than in cell membranes Lipid droplets can act as antioxidant organelles that protect Drosophila neural stem cells from hypoxia-triggered ROS. They sequester polyunsaturated fatty acids away from plasma membranes, thereby shielding these lipids from harmful peroxidation that would otherwise compromise proliferation.