Abstract
Autophagy, a process of cellular self-digestion, delivers intracellular components including superfluous and dysfunctional proteins and organelles to the lysosome for degradation and recycling and is important to maintain cellular homeostasis. In recent decades, autophagy has been found to help fight against a variety of human diseases, but, at the same time, autophagy can also promote the procession of certain pathologies, which makes the connection between autophagy and diseases complex but interesting. In this review, we summarize the advances in understanding the roles of autophagy in human diseases and the therapeutic methods targeting autophagy and discuss some of the remaining questions in this field, focusing on cancer, neurodegenerative diseases, infectious diseases and metabolic disorders.
Highlights
Introduction to AutophagyAutophagy is a conserved process from yeast to human, in which parts of the cytoplasm are transported to the lysosome for degradation and recycling
For a better understanding of how selective autophagy is related to disease, here we provide a brief introduction about the mechanism of mitophagy (Figure 1B)
Because autophagy is critical for the degradation of protein aggregates and maintaining cellular homeostasis, it is not surprising to see that autophagy has a close connection with neurodegeneration: autophagy is responsible for the clearance of accumulated proteins, and this role is important in non-dividing cells
Summary
Autophagy is a conserved process from yeast to human, in which parts of the cytoplasm are transported to the lysosome (the vacuole in fungi and plants) for degradation and recycling. The phagophore closes and forms a double-membrane autophagosome, which fuses with an endosome (not shown) and/or a lysosome; the autophagic cargos are degraded and the breakdown products are released back into the cytosol. PRKN mediated the ubiquitination of OMM proteins, which bind to autophagy receptors, targeting the mitochondria to a phagophore via interaction with an Atg8-family protein. Approximately 40% of proteins contain a KFERQ-like motif [33], indicating that CMA functions as an important lysosome-dependent protein degradation pathway Along these lines, CMA is involved in many different human pathologies, in neurodegenerative diseases [33,34,35], which will be discussed in later sections. We discuss the role of autophagy in four types of disease and the corresponding autophagy-targeting therapies
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