Circadian clock protein BMAL1 broadly influences autophagy and endolysosomal function in astrocytes

Depletion of the core clock protein BMAL1 in astrocytes leads to disrupted endolysosome function and increased accumulation of organelles.

• Astrocyte-specific deletion of BMAL1 results in a unique activation phenotype that disrupts circadian function.
• In vitro, astrocytes lacking BMAL1 show increased processes like endocytosis and lysosome-dependent protein cleavage.
• Electron microscopy reveals accumulation of autophagosome-like structures in the brains of astrocyte-specific knockout mice.
• Transcriptional analysis indicates a broad dysregulation of lysosome function pathways in astrocytes from both young and aged knockout mice.
• Findings suggest a potential link between neurodegeneration and endolysosome dysfunction related to BMAL1 regulation.

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