期刊
NATURE REVIEWS MOLECULAR CELL BIOLOGY
卷 24, 期 3, 页码 167-185出版社
NATURE PORTFOLIO
DOI: 10.1038/s41580-022-00542-2
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Autophagy is a process that degrades various intracellular elements, either non-selectively or selectively. Selective autophagy is involved in degrading specific targets such as damaged organelles, aggregated proteins, or invading bacteria, and plays a crucial role in cellular quality control. Recent progress in understanding the mechanisms of selective autophagy in mammals has the potential to enhance cellular quality control capabilities and alleviate pathology.
Autophagy is a process that targets various intracellular elements for degradation. Autophagy can be non-selective - associated with the indiscriminate engulfment of cytosolic components - occurring in response to nutrient starvation and is commonly referred to as bulk autophagy. By contrast, selective autophagy degrades specific targets, such as damaged organelles (mitophagy, lysophagy, ER-phagy, ribophagy), aggregated proteins (aggrephagy) or invading bacteria (xenophagy), thereby being importantly involved in cellular quality control. Hence, not surprisingly, aberrant selective autophagy has been associated with various human pathologies, prominently including neurodegeneration and infection. In recent years, considerable progress has been made in understanding mechanisms governing selective cargo engulfment in mammals, including the identification of ubiquitin-dependent selective autophagy receptors such as p62, NBR1, OPTN and NDP52, which can bind cargo and ubiquitin simultaneously to initiate pathways leading to autophagy initiation and membrane recruitment. This progress opens the prospects for enhancing selective autophagy pathways to boost cellular quality control capabilities and alleviate pathology. Selective autophagy engages several cargo receptors that target specific, potentially toxic, content (damaged organelles, protein aggregates, pathogens) for lysosomal degradation. Understanding of the mechanisms governing this process in mammals has expanded in recent years, opening the prospects for enhancing selective autophagy to boost cellular quality control capabilities.
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