How protein recycling systems protect the cell's protein balance

Disruption of proteostasis is a hallmark of aging and is associated with various pathologies.

• The ubiquitin-proteasome system and autophagy are key pathways that maintain proteome integrity, especially under stress.
• These two systems operate as an interconnected network rather than as separate processes.
• Coordination between UPS and autophagy is governed by a shared molecular language involving ubiquitin signals and shuttle proteins.
• Quality control is spatially organized through specific cellular compartments and phase-separated degradation hubs.
• Temporal regulation of these pathways is influenced by stress-responsive signaling that alters proteolytic activity.

Simplified