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Initial Steps in Mammalian Autophagosome Biogenesis

During the last decade, autophagy has been pointed out as a central process in cellular homeostasis with the consequent implication in most cellular settings and human diseases pathology. At present, there is significant data available about molecular mechanisms that regulate autophagy. Nevertheless...

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Autores principales: Grasso, Daniel, Renna, Felipe Javier, Vaccaro, Maria Ines
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206277/
https://www.ncbi.nlm.nih.gov/pubmed/30406104
http://dx.doi.org/10.3389/fcell.2018.00146
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author Grasso, Daniel
Renna, Felipe Javier
Vaccaro, Maria Ines
author_facet Grasso, Daniel
Renna, Felipe Javier
Vaccaro, Maria Ines
author_sort Grasso, Daniel
collection PubMed
description During the last decade, autophagy has been pointed out as a central process in cellular homeostasis with the consequent implication in most cellular settings and human diseases pathology. At present, there is significant data available about molecular mechanisms that regulate autophagy. Nevertheless, autophagy pathway itself and its importance in different cellular aspects are still not completely clear. In this article, we are focused in four main aspects: (a) Induction of Autophagy: Autophagy is an evolutionarily conserved mechanism induced by nutrient starvation or lack of growth factors. In higher eukaryotes, autophagy is a cell response to stress which starts as a consequence of organelle damage, such as oxidative species and other stress conditions. (b) Initiation of Autophagy; The two major actors in this signaling process are mTOR and AMPK. These multitasking protein complexes are capable to summarize the whole environmental, nutritional, and energetic status of the cell and promote the autophagy induction by means of the ULK1-Complex, that is the first member in the autophagy initiation. (c) ULK1-Complex: This is a highly regulated complex responsible for the initiation of autophagosome formation. We review the post-transductional modifications of this complex, considering the targets of ULK1. (d)The mechanisms involved in autophagosome formation. In this section we discuss the main events that lead to the initial structures in autophagy. The BECN1-Complex with PI3K activity and the proper recognition of PI3P are one of these. Also, the transmembrane proteins, such as VMP1 and ATG9, are critically involved. The membrane origin and the cellular localization of autophagosome biogenesis will be also considered. Hence, in this article we present an overview of the current knowledge of the molecular mechanisms involved in the initial steps of mammalian cell autophagosome biogenesis.
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spelling pubmed-62062772018-11-07 Initial Steps in Mammalian Autophagosome Biogenesis Grasso, Daniel Renna, Felipe Javier Vaccaro, Maria Ines Front Cell Dev Biol Physiology During the last decade, autophagy has been pointed out as a central process in cellular homeostasis with the consequent implication in most cellular settings and human diseases pathology. At present, there is significant data available about molecular mechanisms that regulate autophagy. Nevertheless, autophagy pathway itself and its importance in different cellular aspects are still not completely clear. In this article, we are focused in four main aspects: (a) Induction of Autophagy: Autophagy is an evolutionarily conserved mechanism induced by nutrient starvation or lack of growth factors. In higher eukaryotes, autophagy is a cell response to stress which starts as a consequence of organelle damage, such as oxidative species and other stress conditions. (b) Initiation of Autophagy; The two major actors in this signaling process are mTOR and AMPK. These multitasking protein complexes are capable to summarize the whole environmental, nutritional, and energetic status of the cell and promote the autophagy induction by means of the ULK1-Complex, that is the first member in the autophagy initiation. (c) ULK1-Complex: This is a highly regulated complex responsible for the initiation of autophagosome formation. We review the post-transductional modifications of this complex, considering the targets of ULK1. (d)The mechanisms involved in autophagosome formation. In this section we discuss the main events that lead to the initial structures in autophagy. The BECN1-Complex with PI3K activity and the proper recognition of PI3P are one of these. Also, the transmembrane proteins, such as VMP1 and ATG9, are critically involved. The membrane origin and the cellular localization of autophagosome biogenesis will be also considered. Hence, in this article we present an overview of the current knowledge of the molecular mechanisms involved in the initial steps of mammalian cell autophagosome biogenesis. Frontiers Media S.A. 2018-10-23 /pmc/articles/PMC6206277/ /pubmed/30406104 http://dx.doi.org/10.3389/fcell.2018.00146 Text en Copyright © 2018 Grasso, Renna and Vaccaro. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Grasso, Daniel
Renna, Felipe Javier
Vaccaro, Maria Ines
Initial Steps in Mammalian Autophagosome Biogenesis
title Initial Steps in Mammalian Autophagosome Biogenesis
title_full Initial Steps in Mammalian Autophagosome Biogenesis
title_fullStr Initial Steps in Mammalian Autophagosome Biogenesis
title_full_unstemmed Initial Steps in Mammalian Autophagosome Biogenesis
title_short Initial Steps in Mammalian Autophagosome Biogenesis
title_sort initial steps in mammalian autophagosome biogenesis
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206277/
https://www.ncbi.nlm.nih.gov/pubmed/30406104
http://dx.doi.org/10.3389/fcell.2018.00146
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