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.