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Mol. Cells 2013; 36(1): 7-16

Published online May 24, 2013

https://doi.org/10.1007/s10059-013-0140-8

© The Korean Society for Molecular and Cellular Biology

Autophagy: A Critical Regulator of Cellular Metabolism and Homeostasis

Stefan W. Ryter, Suzanne M. Cloonan, and Augustine M. K. Choi

Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

Received: May 3, 2013; Accepted: May 6, 2014

Abstract

Autophagy is a dynamic process by which cytosolic material, including organelles, proteins, and pathogens, are sequestered into membrane vesicles called autophagosomes, and then delivered to the lysosome for degradation. By recycling cellular components, this process provides a mechanism for adaptation to starvation. The regulation of autophagy by nutrient signals involves a complex network of proteins that include mammalian target of rapamycin, the class III phosphatidylinositol-3 kinase/Beclin 1 complex, and two ubiquitin-like conjugation systems. Additionally, autophagy, which can be induced by multiple forms of chemical and physical stress, including endoplasmic reticulum stress, and hypoxia, plays an integral role in the mammalian stress response. Recent studies indicate that, in addition to bulk assimilation of cytosol, autophagy may proceed through selective pathways that target distinct cargoes to autophagosomes. The principle homeostatic functions of autophagy include the selective clearance of aggregated protein to preserve proteostasis, and the selective removal of dysfunctional mitochondria (mitophagy). Additionally, autophagy plays a central role in innate and adaptive immunity, with diverse functions such as regulation of inflammatory responses, antigen presentation, and pathogen clearance. Autophagy can preserve cellular function in a wide variety of tissue injury and disease states, however, maladaptive or pro-pathogenic outcomes have also been described. Among the many diseases where autophagy may play a role include proteopathies which involve aberrant accumulation of proteins (e.g., neurodegenerative disorders), infectious diseases, and metabolic disorders such as diabetes and metabolic syndrome. Targeting the autophagy pathway and its regulatory components may eventually lead to the development of therapeutics.

Keywords autophagy, innate immunity, metabolism, mitophagy, neurodegeneration, proteostasis

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Minireview

Mol. Cells 2013; 36(1): 7-16

Published online July 31, 2013 https://doi.org/10.1007/s10059-013-0140-8

Copyright © The Korean Society for Molecular and Cellular Biology.

Autophagy: A Critical Regulator of Cellular Metabolism and Homeostasis

Stefan W. Ryter, Suzanne M. Cloonan, and Augustine M. K. Choi

Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

Received: May 3, 2013; Accepted: May 6, 2014

Abstract

Autophagy is a dynamic process by which cytosolic material, including organelles, proteins, and pathogens, are sequestered into membrane vesicles called autophagosomes, and then delivered to the lysosome for degradation. By recycling cellular components, this process provides a mechanism for adaptation to starvation. The regulation of autophagy by nutrient signals involves a complex network of proteins that include mammalian target of rapamycin, the class III phosphatidylinositol-3 kinase/Beclin 1 complex, and two ubiquitin-like conjugation systems. Additionally, autophagy, which can be induced by multiple forms of chemical and physical stress, including endoplasmic reticulum stress, and hypoxia, plays an integral role in the mammalian stress response. Recent studies indicate that, in addition to bulk assimilation of cytosol, autophagy may proceed through selective pathways that target distinct cargoes to autophagosomes. The principle homeostatic functions of autophagy include the selective clearance of aggregated protein to preserve proteostasis, and the selective removal of dysfunctional mitochondria (mitophagy). Additionally, autophagy plays a central role in innate and adaptive immunity, with diverse functions such as regulation of inflammatory responses, antigen presentation, and pathogen clearance. Autophagy can preserve cellular function in a wide variety of tissue injury and disease states, however, maladaptive or pro-pathogenic outcomes have also been described. Among the many diseases where autophagy may play a role include proteopathies which involve aberrant accumulation of proteins (e.g., neurodegenerative disorders), infectious diseases, and metabolic disorders such as diabetes and metabolic syndrome. Targeting the autophagy pathway and its regulatory components may eventually lead to the development of therapeutics.

Keywords: autophagy, innate immunity, metabolism, mitophagy, neurodegeneration, proteostasis

Mol. Cells
May 31, 2023 Vol.46 No.5, pp. 259~328
COVER PICTURE
The alpha-helices in the lamin filaments are depicted as coils, with different subdomains distinguished by various colors. Coil 1a is represented by magenta, coil 1b by yellow, L2 by green, coil 2a by white, coil 2b by brown, stutter by cyan, coil 2c by dark blue, and the lamin Ig-like domain by grey. In the background, cells are displayed, with the cytosol depicted in green and the nucleus in blue (Ahn et al., pp. 309-318).

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