An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis

Mari, Muriel; Griffith, Janice; Rieter, Ester; Krishnappa, Lakshmi; Klionsky, Daniel J.; Reggiori, Fulvio

doi:10.1083/jcb.200912089

Cited by 430 publications

(465 citation statements)

References 55 publications

(137 reference statements)

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“…Although evidence supports the idea that nucleation of the isolation membrane occurs at a distinct site emanating from the endoplasmic reticulum (ER), termed the omegasome 17 , other sources of membrane contribute to autophagosome formation, including ER-Golgi intermediate compartments, ERmitochondri a junctions, mitochondria, endosomes and the plasma membrane [17][18][19][20][21][22] . Taken together, these studies highlight the complexities of autophagy initiation in mammals.…”

Section: Overview Of the Autophagic Pathwaymentioning

confidence: 99%

Autophagy at the crossroads of catabolism and anabolism

Kaur

Debnath

2015

Nat Rev Mol Cell Biol

843

801

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Section: Overview Of the Autophagic Pathwaymentioning

confidence: 99%

Autophagy at the crossroads of catabolism and anabolism

Kaur

Debnath

2015

Nat Rev Mol Cell Biol

843

801

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“…Nevertheless, fusion of Atg9 vesicles may provide the membrane platform that matures into the isolation membrane. Immunoelectron microscopy analysis in another study detected Atg9 in clusters of small vesicles and tubules, and it was proposed that the isolation membrane may be initiated by the fusion of these clustered vesicles/tubules [89]. The Atg9 vesicle fusion mechanism may involve the yeast Rab protein Ypt1 and its GEF complex (the TRAPP III complex), which are required for autophagy and were identified in purified Atg9 vesicles [90,91].…”

Section: Atg9 Vesicles As a Membrane Sourcementioning

confidence: 99%

A current perspective of autophagosome biogenesis

2013

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Autophagy is a bulk degradation system induced by cellular stresses such as nutrient starvation. Its function relies on the formation of double-membrane vesicles called autophagosomes. Unlike other organelles that appear to stably exist in the cell, autophagosomes are formed on demand, and once their formation is initiated, it proceeds surprisingly rapidly. How and where this dynamic autophagosome formation takes place has been a long-standing question, but the discovery of Atg proteins in the 1990's significantly accelerated our understanding of autophagosome biogenesis. In this review, we will briefly introduce each Atg functional unit in relation to autophagosome biogenesis, and then discuss the origin of the autophagosomal membrane with an introduction to selected recent studies addressing this problem.

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“…In yeast cells, Atg9 is a transmembrane protein that transits between the PAS and peripheral sites ( Figure 3); the latter have been termed Atg9 reservoirs or tubulovesicular clusters, and are proposed to represent sites from which membrane is delivered to the forming phagophore [49,63,85], although the exact role of Atg9 in this process is not clear. Atg9 is proposed to consist of six transmembrane domains, with both the amino and carboxyl termini exposed in the cytosol.…”

Section: Yeast Atg9mentioning

confidence: 99%

“…Rather, after nucleation the phagophore grows through the addition of membrane from one or more donor sources [1,47]; however, the origin of the phagophore membrane is still under debate. Various lines of data suggest a role for almost every membrane compartment in contributing to formation of the autophagosome, including the ER, mitochondria, the Golgi apparatus and the plasma membrane [48][49][50][51][52]. As discussed above, there is no absolute equivalent of the yeast PAS in mammalian cells.…”

Section: Origin Of the Phagophorementioning

confidence: 99%

The machinery of macroautophagy

et al. 2013

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Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.

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An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis

Abstract: A reservoir of Atg9-containing vesicles and tubules provides the initial membranes necessary for autophagophore formation in yeast.

Cited by 430 publications

References 55 publications

Autophagy at the crossroads of catabolism and anabolism

Autophagy at the crossroads of catabolism and anabolism

A current perspective of autophagosome biogenesis

The machinery of macroautophagy

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