Abstract
Eukaryotic cells can massively transport their own cytoplasmic contents into a lytic compartment, the vacuole/lysosome, for recycling through a conserved system called autophagy. The key process in autophagy is the sequestration of cytoplasmic contents within a double-membrane structure, the autophagosome. Autophagosome formation requires the elaborate cooperation of Atg (autophagy-related) proteins and lipid molecules. Phosphorylation of phosphatidylinositol (PtdIns) by a PtdIns 3-kinase, Vps34, is a key step in coordinating Atg proteins and lipid molecules. Vps34 forms two distinct protein complexes, only one of which is involved in generating autophagic membranes. Upon induction of autophagy, PtdIns(3)P, the enzymatic product of PtdIns 3-kinase, is massively transported into the lumen of the vacuole via autophagy. PtdIns(3)P is enriched on the inner membrane of the autophagosome. PtdIns(3)P recruits the Atg18−Atg2 complex and presumably other Atg proteins to autophagic membranes, thereby coordinating lipid molecules and Atg proteins.
Highlights
ATP AMP + PPi is the sole membrane-spanning protein among the 18 Atg proteins that are essential for autophagosome formation [14] and is one of the key molecules that links proteins and lipid molecules
The lipid kinase activity of Vps34 is essential for autophagosome formation as introducing a lipid kinase-dead form of Vps34 does not restore the autophagic activity of vps34Δ cells [23]
Vps15, Vps30/Atg6, and Atg14, which form a complex with Vps34, are essential for autophagy [22, 24]
Summary
Eukaryotic cells are equipped with a self-digesting system called macroautophagy (hereafter, autophagy). Using this system, cells can degrade a portion of their cytoplasmic contents, occasionally including organelles, within a lytic compartment called the vacuole or lysosome. Autophagy involves unique membrane dynamics, which has been predominantly shown through detailed electron microscopic analyses of starved yeast cells [5, 6]. The autophagosome fuses with a vacuole or lysosome, where the inner membrane structure is released into the lumen as the autophagic body and is degraded (Figure 1) [5, 7]. There are unsolved problems including the source of the autophagosome membrane, mechanism of membrane expansion, determinant of membrane curvature, and differentiation of the inner and outer membranes
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