Abstract

All cells are endowed with two catabolic pathways for degrading protein: the ubiquitinproteasome system (UPS) and autophagy. While these routes of protein degradation were long considered to be parallel and complementary systems, new evidence has revealed interaction between the UPS and autophagy, suggesting a coordinated relationship that becomes critical in times of cellular stress. Here we introduce the basics and parallels of the UPS and autophagy, review the evidence for cross-regulation of the two systems, and highlight their emerging coordinated relationship. Throughout, we review the evidence suggesting that impairment of autophagy could contribute to the initiation or progression of age-related neurodegeneration.