The integration of protein and organelle degradation systems and its pathophysiological functions.

Electron tomography has revealed the ultrastructural basis of how ubiquitin-proteasome and autophagy systems coordinate to partition proteins and organelles for degradation under stress.

• Why it matters: Cellular homeostasis depends on timely removal of misfolded proteins, aberrant complexes, and damaged organelles, but the rules for how these two pathways share substrates are not fully clear.
• What they did: This Review synthesizes mechanisms for substrate sequestration, spatial-temporal organization of degradation machinery, compensatory responses when one pathway is impaired, and links to the unfolded protein response, including ER phagy and mitophagy.
• The result: Defects in these integrated degradation networks are discussed as contributing to ageing, cancer, neurodegeneration, and other pathologies, offering a framework for understanding proteostasis failure.

AI summary of the abstract · may contain errors · not medical advice · read the paper.