Das Anurag, Rivas-Serna Irma Magaly, Kumar Ankur, Kalita Hia, Sherpa Lakpa, Vaughen John P, Bai Hua
Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Interdepartmental Neuroscience PhD program, Iowa State University, Ames, IA 50011, USA.
bioRxiv. 2025 Jun 25:2025.06.23.661129. doi: 10.1101/2025.06.23.661129.
Peroxisomes are critical organelles that detoxify wastes while also catabolizing and anabolizing lipids. How peroxisomes coordinate protein import and support metabolic functions across complex tissues and timescales remains poorly understood . Using the brain, we discover a striking enrichment of peroxisomes in the neuronal soma and the cortex glia that enwrap them. Unexpectedly, import of peroxisomal proteins into cortex glia, but not neurons, dramatically oscillated across time and peaked in the early morning. Rhythmic peroxisomal import in cortex glia autonomously required the circadian clock and Peroxin 5 (Pex5; peroxisomal biogenesis factor 5 homolog), with endogenous Pex5 protein peaking in the morning. Notably, removing in cortex glia severely reduced sleep while concomitantly causing aberrant lipid metabolism characterized by ectopic lipid droplets and increases across multiple lipid families. Thus, the circadian import of peroxisomal proteins via Pex5 in cortex glia is essential for lipid homeostasis and organismal behavior.
过氧化物酶体是重要的细胞器，可对废物进行解毒，同时分解和合成脂质。过氧化物酶体如何在复杂的组织和时间尺度上协调蛋白质输入并支持代谢功能，目前仍知之甚少。通过研究大脑，我们发现过氧化物酶体在神经元胞体和包裹它们的皮质神经胶质细胞中显著富集。出乎意料的是，过氧化物酶体蛋白向皮质神经胶质细胞而非神经元的输入随时间剧烈振荡，并在清晨达到峰值。皮质神经胶质细胞中有节律的过氧化物酶体输入自主地需要生物钟和过氧化物酶5（Pex5；过氧化物酶体生物发生因子5同源物），内源性Pex5蛋白在早晨达到峰值。值得注意的是，去除皮质神经胶质细胞中的Pex5会严重减少睡眠，同时导致异常的脂质代谢，其特征是出现异位脂滴，并且多个脂质家族的含量增加。因此，通过Pex5在皮质神经胶质细胞中进行的过氧化物酶体蛋白的昼夜节律输入对于脂质稳态和机体行为至关重要。
