Survival strategies of a sterol auxotroph
Survival strategies of a sterol auxotroph
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DOI：
10.1242/dev.044560
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发表时间：
2010-11-01
期刊：
影响因子：
4.6
通讯作者：
Eaton, Suzanne
中科院分区：
文献类型：
--
作者：
Carvalho, Maria;Schwudke, Dominik;Eaton, Suzanne
真核细胞膜中的高固醇浓度被认为会影响膜的性质，如渗透性、流动性和微区形成。果蝇不能合成甾醇，但需要它们来发育。这是否仅仅反映了类固醇激素生物合成中对甾醇的需求，或者大部分膜甾醇在果蝇中也是必不可少的？如果后者是真的，那么它们如何在固醇可用性的波动中生存并维持膜稳态？在这里，我们表明，果蝇需要大量的膜甾醇和类固醇激素，以完成成人的发展。当固醇的可用性受到限制时，果蝇幼虫调节其生长以将膜固醇水平维持在严格的限度内。当膳食固醇下降到最低阈值以下时，幼虫以可逆的方式停止生长和发育。引人注目的是，除了神经系统外，大多数组织中被捕幼虫的膜固醇水平显著降低（平均下降六倍）。因此，甾醇是维持细胞活力所需的基本膜生物物理性质的必需品;当甾醇不可用时，这些功能可以由非甾醇脂质执行。然而，大量的膜甾醇可能在发育过程中的特定组织中具有重要功能。在固醇水平下降的组织中，鞘脂的总体水平增加，不同鞘脂变体的比例改变。当膜固醇水平低时，这些变化允许存活，但不允许生长。甾醇和鞘脂之间的这种关系可能是膜稳态的古老而保守的原则。
The high sterol concentration in eukaryotic cell membranes is thought to influence membrane properties such as permeability, fluidity and microdomain formation. Drosophila cannot synthesize sterols, but do require them for development. Does this simply reflect a requirement for sterols in steroid hormone biosynthesis, or is bulk membrane sterol also essential in Drosophila? If the latter is true, how do they survive fluctuations in sterol availability and maintain membrane homeostasis? Here, we show that Drosophila require both bulk membrane sterol and steroid hormones in order to complete adult development. When sterol availability is restricted, Drosophila larvae modulate their growth to maintain membrane sterol levels within tight limits. When dietary sterol drops below a minimal threshold, larvae arrest growth and development in a reversible manner. Strikingly, membrane sterol levels in arrested larvae are dramatically reduced (dropping sixfold on average) in most tissues except the nervous system. Thus, sterols are dispensable for maintaining the basic membrane biophysical properties required for cell viability; these functions can be performed by non-sterol lipids when sterols are unavailable. However, bulk membrane sterol is likely to have essential functions in specific tissues during development. In tissues in which sterol levels drop, the overall level of sphingolipids increases and the proportion of different sphingolipid variants is altered. These changes allow survival, but not growth, when membrane sterol levels are low. This relationship between sterols and sphingolipids could be an ancient and conserved principle of membrane homeostasis.