Cross-link between the ubiquitin-proteasome system (UPS) and autophagy in the regulation of mitophagy

Official URL: http://risc01.sabanciuniv.edu/record=b2103060 (Table of Contents)

Autophagy and the ubiquitin–proteasome system (UPS) are the two major intracellular protein quality control and recycling mechanisms that are responsible for cellular homeostasis in eukaryotes. Ubiquitylation is utilized as a degradation signal for both systems, however, the two system differ in terms of their mode of actions. The UPS is responsible for the degradation of short-lived proteins and soluble unfolded/misfolded proteins whereas autophagy eliminates rather long-lived proteins, insoluble protein aggregates and even whole organelles (e.g., mitochondria, peroxisomes) and pathogenic invaders (e.g., bacteria). In addition to an indirect connection between the two systems through ubiquitylated proteins, recent data indicate the presence of functional connections and reciprocal regulation mechanisms between these degradation pathways. In this thesis work, we have characterized and analyzed novel and direct links between the UPS and autophagy. Autophagy of mitochondria was chosen as a model to study the interaction and crosstalk between autophagy and the UPS. Functional consequences of these findings will be presented and discussed in detail.