Autophagosome formation: core machinery and adaptations

Abstract

Eukaryotic cells employ autophagy to degrade damaged or obsolete organelles and proteins. Central to this process is the formation of autophagosomes, double-membrane vesicles responsible for delivering cytoplasmic material to lysosomes. In the past decade many autophagy-related genes, ATG, have been identified that are required for selective and/or nonselective autophagic functions. In all types of autophagy, a core molecular machinery has a critical role in forming sequestering vesicles, the autophagosome, which is the hallmark morphological feature of this dynamic process. Additional components allow autophagy to adapt to the changing needs of the cell.

Cellular and molecular mechanisms in liver fibrogenesis

“…Autophagy machinery recognizes the "cargo" to be degraded through the cytosolic adaptor protein P62/sequestosome 1 that binds to the microtubule-associated protein 1 light chain 3 (LC3) in order to deliver the cargo for autophagic degradation [93,94].…”

“…It requires the involvement of class III phosphatidylinositol 3-kinase (PI3K) complex, which also include the PI3K vacuolar protein sorting 34 (Vps34), beclin1, Atg 14 and p150, with beclin 1 being inactivated in normal conditions through its binding to the antiapoptotic protein Bcl2 (B-cell lymphoma/leukemia-2) [93,94]. The PI3K complex then recruits two ubiquitin-like conjugation complexes formed by several Atg proteins, one needed for autophagosome formation and the second for its elongation, both involving a key player like Atg7.…”

“…A very complex series of reactions, leads finally to the binding of these complexes to the nascent phagophore and then the formation of autophagosomes [93,94].…”

Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates

“…1 In this paper, macroautophagy will be simply referred to as autophagy. Autophagy may be characterized by nonspecific sequestration and degradation of the bulk cytoplasm, a process that recycles essential building blocks for production of macromolecules under conditions where nutrients are limited.…”

“…1 Autophagy process initiates with the formation of a distinct structure referred to as the phagophore that extends its ends and seals in circle to form the AP. APs can fuse with various endosomal vesicles, forming amphisomes, and eventually fuse with lysosomes to form autolysosomes, where degradation of contents takes place.…”