A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis

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…

• NS
  National Science Foundation
• HH
  Howard Hughes Medical Institute
• NI
  National Institutes of Health

  Awards: R01DK120757, T32HL007953, T32MH014654
• NH
  National Heart, Lung, and Blood Institute

  Award: T32HL007953
• NI
  National Institute of Mental Health

  Award: K08 NS131602