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ISRN Cell Biology
Volume 2012 (2012), Article ID 927064, 11 pages
http://dx.doi.org/10.5402/2012/927064
Review Article

Autophagy Mechanism, Regulation, Functions, and Disorders

Department of Pediatrics, University of California at Irvine, 2501 Hewitt Hall, Irvine, CA 92697, USA

Received 31 May 2012; Accepted 30 July 2012

Academic Editors: D. Arnoult, D. Bouvard, and A. Chiarini

Copyright © 2012 Mallikarjun Badadani. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Autophagy is a self-digesting mechanism responsible for removal of damaged organelles, malformed proteins during biosynthesis, and nonfunctional long-lived proteins by lysosome. Autophagy has been divided into three general types depending on the mechanism by which intracellular materials are delivered into lysosome for degradation that is, microautophagy, chaperone-mediated autophagy (CMA), and macroautophagy. In microautophagy cytoplasm material is sequestered through direct invagination to the lysosomal membrane. Whereas in CMA proteins flagged with pentapeptide motif (KFERQ) were selectively degraded through direct translocation into lysosome. Macroautophagy involves the formation of subcellular double-membrane-bound structures called autophagosomes that contain degradable contents of cytoplasm materials and deliver them into lysosomes for breakdown by lysosomal enzymes. The molecular mechanism of autophagy involves several conserved Atg (autophagy-related) proteins. Systems produce modified complexes Atg8-PE and Atg5-Atg12-Atg16 as autophagy regulators. Autophagy is activated in response to diverse stress and physiological conditions. For example, food deprivation, hyperthermia, and hypoxia are mediated by factors like insulin/IGF-1, m-TOR signaling, FOXO transcription factors, and chaperones. The perturbance in autophagy may lead to several types of cancers, myopathies, and neuromuscular disorders. Several autophagy inducers and inhibitors like 3-methyladenine (3-MA), bafilomycin A1, LY294002 (LY), and Velcade have been used to treat disease is an intense field of study.