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bioRxiv · 10.1101/2025.06.23.661129

Peroxisomal import is circadian in glia and regulates sleep and lipid metabolism

Das, A.·Serna, I. M. R.·Kumar, A.·Kalita, H.·Sherpa, L.·Vaughen, J. P.·Bai, H.
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Abstract

Peroxisomes are critical organelles that detoxify cellular waste while also catabolizing and anabolizing lipids. How peroxisomes coordinate protein import and support metabolic functions across complex tissues and timescales remains poorly understood in vivo. Using the Drosophila 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, 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 import persistently elevated in clock mutants. Notably, reducing Pex5 in cortex glia, but not neurons, caused hyperactivity and reduced total sleep. Moreover, brain lipid metabolism was dramatically altered upon Pex5 knockdown, with glia impacting sphingolipids and triacylglycerols, and neurons impacting phospholipids. The cell-type specificity of these Pex5 phenotypes highlights unique roles for peroxisomal import in both sleep and lipid metabolism in the brain.

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Das, A., Serna, I. M. R., Kumar, A., Kalita, H., Sherpa, L., Vaughen, J. P., Bai, H.. 2025-06-25. Peroxisomal import is circadian in glia and regulates sleep and lipid metabolism. https://doi.org/10.1101/2025.06.23.661129

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