Abstract
Autophagy contributes to cellular homeostasis through the degradation of various intracellular targets such as proteins, organelles and microbes. This relates autophagy to various diseases such as infections, neurodegenerative diseases and cancer. A central component of the autophagy machinery is the class III phosphatidylinositol 3-kinase (PI3K-III) complex, which generates the signaling lipid phosphatidylinositol 3-phosphate (PtdIns3P). The catalytic subunit of this complex is the lipid-kinase VPS34, which associates with the membrane-targeting factor VPS15 as well as the multivalent adaptor protein BECLIN 1. A growing list of regulatory proteins binds to BECLIN 1 and modulates the activity of the PI3K-III complex. Here we discuss the regulation of BECLIN 1 by several different types of ubiquitination, resulting in distinct polyubiquitin chain linkages catalyzed by a set of E3 ligases. This contribution is part of the Special Issue “Ubiquitin System”.
Highlights
Macroautophagy, hereafter referred to as autophagy, is a cell-protective mechanism that is based on the degradation of intracellular targets within the lytic compartment of the cell, which is the lysosome in mammals and the vacuole in yeasts and plants
The known E3 ligases and DUB systems concerning the ubiquitination of BECLIN 1 have been identified in single-focused studies
It will be of interest to combine the single outcomes of the studies in order to generate a coherent picture of the mechanistic network that regulates BECLIN 1 function
Summary
Macroautophagy, hereafter referred to as autophagy, is a cell-protective mechanism that is based on the degradation of intracellular targets within the lytic compartment of the cell, which is the lysosome in mammals and the vacuole in yeasts and plants This enables the general recycling of macromolecules during starvation as well as the selective elimination of potential harmful structures, such as protein aggregates, damaged organelles or phagocytosed pathogens. At the end of the elongation phase (III), the targets are completely engulfed in the autophagosome This maturation of the autophagosome depends on two ubiquitin-like conjugation systems, namely ATG12 (autophagy-related 12) and LC3 (1A/1B light chain 3) (Atg in yeast), as well as on the VPS34 lipid kinase complex. The autophagosome fuses with the lysosome, depending on the small GTPase RAB7 (ras-related in brain 7), and forms the autolysosome, in which the targets are hydrolysed (IV) [4]
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