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Autophagy-driven Presynaptic Reorganization as a Molecular Signature of Brain Resilience

ABSTRACT: Neural circuits must maintain functional stability while remaining adaptable to changing demands and stress. This balance is thought to rely on plasticity programs that integrate molecular and activity-dependent signals to structurally and functionally reconfigure synapses; however, the underlying mechanisms remain poorly understood. Here, we demonstrate that targeted impairment of autophagy in the Drosophila mushroom body (MB) induces brain-wide post-transcriptional remodeling at presynaptic active zones (AZ). This remodeling is characterized by the selective upregulation of AZ scaffold proteins, reduced levels of calcium channel subunits, and increased abundance of Shaker-type potassium channels. Functionally, this AZ remodeling program enhances resilience to local autophagy disruption, as evidenced by increased sleep and extended lifespan. Moreover, MB-specific autophagy impairment leads to a non-cell-autonomous accumulation of autophagic substrates across the brain, indicating systemic propagation of proteostatic stress. Together, our findings identify MB autophagy as a key regulator of synaptic architecture and sleep-associated resilience, and establish a genetically tractable model for how localized stress signals can drive brain-wide adaptive responses through synaptic reprogramming.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Brain

SUBMITTER: Pin-Lian Jiang

LAB HEAD: Fan Liu

PROVIDER: PXD076163 | Pride | 2026-07-06

REPOSITORIES: Pride

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			Action	DRS
	A2_20260220_FAIMS_JPL_CH26-3_fly_ubi_ct_1_A.raw	Raw
	A2_20260220_FAIMS_JPL_CH26-3_fly_ubi_ct_1_B.raw	Raw
	A2_20260220_FAIMS_JPL_CH26-3_fly_ubi_ct_2_A.raw	Raw
	A2_20260220_FAIMS_JPL_CH26-3_fly_ubi_ct_2_B.raw	Raw
	A2_20260220_FAIMS_JPL_CH26-3_fly_ubi_ct_3_A.raw	Raw

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Autophagy-driven Presynaptic Reorganization as a Molecular Signature of Brain Resilience

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