Autophagy is a process tightly regulated by various autophagy-related proteins. Whereas non-selective autophagy is triggered when the cell is under starvation, selective autophagy is involved in eliminating dysfunctional organelles, misfolded and/or ubiquitylated proteins, and intracellular pathogens. These components are recognized by autophagy receptors such as p62/SQSTM1, and delivered to phagophores.
Selective autophagy receptors usually have some common domains, such as LC3-interacting-region (LIR) motif, a specific cargo interacting domain. Autophagy receptors recognize and recruit specific cargoes to autophagy signaling for degradation in ubiquitin-dependent and -independent manners, and their functions are regulated by protein modifications, for example, phosphorylation and ubiquitination. The role for autophagy receptors in selective autophagy has been well established and it is particularly important in postmitotic cells.
Autophagy receptors can be grouped based on their specific cargo-binding domains. Fundamental different principals have been employed for the use of these binding domains in selective autophagy ranging from protein-specific interaction domains via posttranslational modification- (PTM-) binding domains to transmembrane domains.
While protein-specific interaction domains yield autophagosomal delivery of only a set of very specialized targets, PTM-specific binding domains, namely, ubiquitin-binding domains, allow for autophagy engagement of a huge variety of proteins. Lastly, by the virtue of membrane embedding, autophagy receptors mediate organelles-specific targeting for selective autophagy.
Different autophagy receptors recognize distinct cargo as substrates and, depending on the nature of the cargo, several selective autophagy pathways have been described: mitochondria (mitophagy), ribosomes (ribophagy), peroxisomes (Pexophagy), endoplasmic reticulum (reticulophagy), nuclear envelope (nucleophagy), liposomes (lipophagy), and lysosomes (lysophagy), etc. Selective autophagy, therefore, plays an important role in the maintenance of cellular homeostasis and is considered a major quality control mechanism of the cell.
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