Autophagy and human disease.
As a conserved cellular degradative pathway in eukaryotes, autophagy relieves cells from various types of stress. There are different forms of autophagy, and the ongoing studies of the molecular mechanisms and cellular functions of these processes are unraveling their significant roles in human health. Currently, the best-studied of these pathways is macroautophagy, which is linked to a range of human disease. For example, as part of the host immune defense mechanism, macroautophagy is activated to eliminate invasive pathogenic bacteria; however, in some cases bacteria subvert this process for their own replication. Autophagy also contributes to endogenous major histocompatibility complex class II antigen presentation, reflecting its role in adaptive immunity. In certain neurodegenerative diseases, which are associated with aggregation-prone proteins, macroautophagy plays a protective role in preventing or reducing cytotoxicity by clearance of the toxic proteins; however, the autophagy-dependent processing of some components correlates with the pathogenesis of certain myopathies. Finally, autophagy acts as a mechanism for tumor suppression, although some cancer cells use it as a cytoprotective mechanism. Thus, a fundamental paradox of autophagy is that it can act to promote both cell survival and cell death, depending on the specific conditions.
Huang
Ju
J
University of Michigan, Life Sciences Institute, Department of Molecular, Cellular and Developmental Biology, Ann Arbor, Michigan 48109 , USA.
Klionsky
Daniel J
DJ
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001343:Autophagy; D004194:Disease; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
D000941:Antigens