The Golgi as an Assembly Line to the Autophagosome

Autophagy is traditionally depicted as a signaling cascade that culminates in the formation of an autophagosome that degrades cellular cargo. However, recent studies have identified myriad pathways and cellular organelles underlying the autophagy process, be it as signaling platforms or through the...

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Bibliographic Details
Published in:Trends in biochemical sciences (Amsterdam. Regular ed.) 2020-06, Vol.45 (6), p.484-496
Main Authors: De Tito, Stefano, Hervás, Javier H., van Vliet, Alexander R., Tooze, Sharon A.
Format: Article
Language:English
Subjects:
adaptor complexes
ATG9A
Autophagosomes - physiology
Autophagy
Autophagy-Related Proteins - physiology
BAR domain
Biological Transport
Endosomes - metabolism
Golgi Apparatus - physiology
Golgi complex
Humans
Lipid Metabolism
Membrane Proteins - physiology
PIP
Vesicular Transport Proteins - physiology
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Summary:Autophagy is traditionally depicted as a signaling cascade that culminates in the formation of an autophagosome that degrades cellular cargo. However, recent studies have identified myriad pathways and cellular organelles underlying the autophagy process, be it as signaling platforms or through the contribution of proteins and lipids. The Golgi complex is recognized as being a central transport hub in the cell, with a critical role in endocytic trafficking and endoplasmic reticulum (ER) to plasma membrane (PM) transport. However, the Golgi is also an important site of key autophagy regulators, including the protein autophagy-related (ATG)-9A and the lipid, phosphatidylinositol-4-phosphate [PI(4)P]. In this review, we highlight the central function of this organelle in autophagy as a transport hub supplying various components of autophagosome formation. The Golgi complex regulates production and delivery of proteins and lipids, and is a site of lipid metabolism needed for autophagy, in particular PI(4)P.ATG9A is the sole transmembrane ATG protein and has a crucial role in the formation of the autophagosome, one new role being the delivery of the metabolizing enzymes of PI to the nascent autophagosome.ATG9A trafficking from the Golgi and recycling endosome is controlled by the coat adaptor complexes AP1, AP2, and AP4, and several BAR-domain containing proteins BIF1, SNX18, and recently Arfaptin2.The control of ATG9A delivery to the forming autophagosome allows in situ PI(4)P production for the initiation of phagophore formation.
ISSN:0968-0004
1362-4326
DOI:10.1016/j.tibs.2020.03.010