Abstract
Autophagy and the ubiquitin–proteasome system (UPS) are the two major intracellular quality control and recycling mechanisms that are responsible for cellular homeostasis in eukaryotes. Ubiquitylation is utilized as a degradation signal by both systems, yet, different mechanisms are in play. The UPS is responsible for the degradation of short-lived proteins and soluble misfolded proteins whereas autophagy eliminates long-lived proteins, insoluble protein aggregates and even whole organelles (e.g., mitochondria, peroxisomes) and intracellular parasites (e.g., bacteria). Both the UPS and selective autophagy recognize their targets through their ubiquitin tags. In addition to an indirect connection between the two systems through ubiquitylated proteins, recent data indicate the presence of connections and reciprocal regulation mechanisms between these degradation pathways. In this review, we summarize these direct and indirect interactions and crosstalks between autophagy and the UPS, and their implications for cellular stress responses and homeostasis.
Highlights
The ubiquitin–proteasome system (UPS) and macroautophagy are two major intracellular protein degradation pathways
Autophagy and the ubiquitin proteasome systems are major degradation systems in mammalian cells that allow recycling of cellular contents ranging from soluble proteins to intracellular organelles
Ubiquitin is a common signal for both the UPS and autophagy
Summary
The ubiquitin–proteasome system (UPS) and macroautophagy (hereafter referred as autophagy) are two major intracellular protein degradation pathways. Selective targets include mitochondria (Okamoto et al, 2009), peroxisomes (Till et al, 2012), lysosomes (Hung et al, 2013), endoplasmic reticulum (ER) (Khaminets et al, 2015), ribosomes (An and Harper, 2018), cytoplasmic protein aggregates (Lamark and Johansen, 2012), pathogenic intracellular invaders (Wileman, 2013) and even certain free proteins and RNAs (Huang et al, 2015) were shown to be targets of selective autophagy By this way, cells control number of the organelles, eliminate dysfunctional components and get rid of potentially harmful aggregates and invaders. The UPS and autophagy are the two major and evolutionarily conserved degradation and recycling systems in eukaryotes Their activities are not interdependent, recent studies show that connections and crosstalks exist between the two systems. We will summarize biological events involving autophagy and the UPS, and discuss molecular details of the crosstalk mechanisms
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