Sleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation that is dependent on prior wake and requires the Drosophila APOE orthologs NLaz and GLaz, which mediate neuron–glia lipid transfer. In turn, a full night of sleep is required for glial lipid clearance, mitochondrial oxidative recovery and maximal neuronal mitophagy. Knockdown of neuronal NLaz causes oxidative stress to accumulate in neurons, and the neuronal mitochondrial integrity protein, Drp1, is required for daily glial lipid accumulation. These data suggest that neurons avoid accumulation of oxidative mitochondrial damage during wake by using mitophagy and passing damage to glia in the form of lipids. We propose that a mitochondrial lipid metabolic cycle between neurons and glia reflects a fundamental function of sleep relevant for brain energy homeostasis.

睡眠被认为可以恢复大脑能量稳态，但尚不清楚这是如何实现的。我们在此表明​​，果蝇神经胶质细胞表现出神经胶质线粒体氧化和脂质积累的日常循环，该循环依赖于先前的唤醒，并且需要果蝇APOE 直系同源物 NLaz 和 GLaz，它们介导神经元-神经胶质细胞脂质转移。反过来，神经胶质脂质清除、线粒体氧化恢复和最大神经元线粒体自噬需要一整夜的睡眠。神经元NLaz的敲低会导致氧化应激在神经元中积累，而神经元线粒体完整性蛋白 Drp1 是日常神经胶质脂质积累所必需的。这些数据表明，神经元通过使用线粒体自噬并将损伤以脂质的形式传递给神经胶质细胞，避免了唤醒期间氧化线粒体损伤的积累。我们提出，神经元和神经胶质细胞之间的线粒体脂质代谢循环反映了与大脑能量稳态相关的睡眠的基本功能。