Regulation of mammalian autophagy in physiology and pathophysiology.

By B. Ravikumar, Sovan Sarkar, J. Davies, M. Futter, M. García-Arencibia, Zeyn W. Green-Thompson, M. Jimenez-Sanchez, Viktor I. Korolchuk, Maike Lichtenberg, S. Luo and 9 more. Physiological Reviews, 2010

1,769 citations recorded by the source corpus.

(Macro)autophagy is a bulk degradation process that mediates the clearance of long-lived proteins and organelles. Autophagy is initiated by double-membraned structures, which engulf portions of cytoplasm. The resulting autophagosomes ultimately fuse with lysosomes, where their contents are degraded. Although the term autophagy was first used in 1963, the field has witnessed dramatic growth in the last 5 years, partly as a consequence of the discovery of key components of its cellular machinery. In this review we focus on mammalian autophagy, and we give an overview of the understanding of its machinery and the signaling cascades that regulate it. As recent studies have also shown that autophagy is critical in a range of normal human physiological processes, and defective autophagy is associated with diverse diseases, including neurodegeneration, lysosomal storage diseases, cancers, and Crohn's disease, we discuss the roles of autophagy in health and disease, while trying to critically evaluate if the coincidence between autophagy and these conditions is causal or an epiphenomenon. Finally, we consider the possibility of autophagy upregulation as a therapeutic approach for various conditions.

Subfields: Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/6d6ec7e7966a54771afe60237e9c88be764e8128

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In Physiology

1. Guido Kroemer
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Citations in the corpus

• Autophagy and autophagy-related proteins in cancer (2020, background): “In diseases, such as neurodegenerative diseases [165, 166], infectious diseases [11, 167, 168], and metabolic diseases [14], dysfunctional autophagy leads to the accumulation of abnormal and damaged proteins and organelles and formation of intracellular aggregates, and then prevents the ability of a”
• Autophagy and aging. (2011, background): “This mechanism may also contribute to autophagy upregulation by endoplasmic reticulum (ER) stress (Ravikumar et al., 2010).”
• Mitophagy: mechanisms, pathophysiological roles, and analysis (2012, neutral): “Keywords: autophagy; mitophagy; Nix; Parkin.”
• Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling (2013, neutral): “…endosome/lysosome marker) starting as early as after 15 min chase and Autophagy, another catabolic process which routes cytosolic proteins to the lysosomes 23,24 , was apparently not involved in LNP-mediated gene silencing as LNPs showed little co-localization with markers of autophagy (Fig S4a-b).”
• Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity (2012, background): “The lysosomal degradation pathways play a vital role in cellular homeostasis, and lysosomal dysfunction has been associated with several disease states, termed lysosomal storage disorders [33,50].”
• Mechanisms of diabetic complications. (2013, background): “Autophagy is a cellular process that is responsible for the breakdown of proteins into their constituent amino acids during times of need, including starvation and metabolic disorders such as diabetes (487).”
• Autophagy modulation as a potential therapeutic target for diverse diseases (2012, neutral): “cAMP–EPAC–PLCε–Ins(1,4,5)P3 and Ca2+–calpain–GSα pathways”
• Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies (2023, background): “is an essential process that maintains cellular homeostasis via the lysosome-dependent degradation of cellular components, such as proteins and organelles, allowing cells to recycle macromolecules 258,259 .”
• Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review (2012, background): “ normal cells, autophagy stimulators may be useful for cancer prevention by enhancing damage mitigation and senescence, while autophagy inhibitors can induce tumorigenesis (White & DiPaola, 2009; Ravikumar et al., 2010; Chen & Karantza, 2011). Network analysis of the regulation of autophagy ”
• Autophagy and apoptosis dysfunction in neurodegenerative disorders. (2014, neutral): “Defective autophagy pathway or alterations in autophagy-related genes is shown in various human pathologies including neurodegenerative and lysosomal storage disorders as well as in various cancers (Mizushima et al., 2008; Ravikumar et al., 2010).”