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Selective Autophagy in Age-Associated Pathologies
Selective autophagy degrades a plethora of autophagic cargo, which is targeted upon specific cellular insults. Defective mitochondria (mitophagy), protein aggregates (aggrephagy) or pathogenic bacteria (xenophagy) are selective autophagy triggers. Atg8 proteins interact and recruit selective autophagic receptors, which contain LIR (LC3-interacting) motifs (W/F/Y-X-X-L/I/V), with upstream negatively charged residues for higher affinity interactions, as well as, post-translational modifications, such as phosphorylation.
Cellular garbage disposal is critical for recycling defective cell constituents, such as proteins and organelles, towards the maintenance of cellular homeostasis. One of the main degradative molecule pathways is autophagy, which is a physiological catabolic process shared by all eukaryotes. Derived from the Greek words ‘auto’ meaning self, and ‘phagy’, meaning eating, autophagy, it was initially considered to be a bulk degradation process, while now its highly selective nature is increasingly appreciated. This self-digestive mechanism relieves the cell from proteotoxic, genotoxic, oxidative and nutrient stress . It is accomplished in an intricate stepwise manner, which leads to clearance of damaged cell constituents, in the degradative organelle, the lysosome. Failure to complete this procedure has been implicated in many age-related diseases. Three main types of autophagy have been characterized in detail: macro-autophagy, henceforth referred to as autophagy, which invariably entails the formation of a double membrane vesicle that fuses with the lysosome; micro-autophagy, where there is direct interaction between the autophagic substrate and the lytic organelle, and chaperone-mediated autophagy (CMA), where autophagic substrates are targeted by chaperones and guided to specific receptors on the lysosome, for degradation.
2. General Autophagy
3. Selective Autophagy
The entry is from 10.3390/metabo11090588
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