Endocytosis and autophagy: exploitation or cooperation? - PubMed (original) (raw)

Review

Endocytosis and autophagy: exploitation or cooperation?

Sharon A Tooze et al. Cold Spring Harb Perspect Biol. 2014.

Abstract

Autophagy is a lysosome-mediated degradative system that is a highly conserved pathway present in all eukaryotes. In all cells, double-membrane autophagosomes form and engulf cytoplasmic components, delivering them to the lysosome for degradation. Autophagy is essential for cell health and can be activated to function as a recycling pathway in the absence of nutrients or as a quality-control pathway to eliminate damaged organelles or even to eliminate invading pathogens. Autophagy was first identified as a pathway in mammalian cells using morphological techniques, but the Atg (autophagy-related) genes required for autophagy were identified in yeast genetic screens. Despite tremendous advances in elucidating the function of individual Atg proteins, our knowledge of how autophagosomes form and subsequently interact with the endosomal pathway has lagged behind. Recent progress toward understanding where and how both the endocytotic and autophagic pathways overlap is reviewed here.

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Figures

Figure 1.

Figure 1.

Autophagy and the endocytic pathway. Autophagosomes form at the PAS (pre-autophagosome structure or phagophore assembly site) and fuse with recycling endosomes, MVBs, and lysosomes (not shown for clarity), becoming an amphisome, which upon further fusion with lysosomes becomes an autolysosome. Not shown are the membrane compartments implicated in the formation of the PAS and autophagosomes (ER, Golgi, mitochondria, and plasma membrane–derived vesicles).

Figure 2.

Figure 2.

Lysosome function and reformation after autophagy. The activity of mTORC1 on the lysosome is coupled with amino acid production and reformation of the lysosome after amino acid starvation (based on data from Lamb et al. 2012).

Figure 3.

Figure 3.

Tethering complexes and small GTPases implicated in endocytosis and autophagy. See text for details.

Figure 4.

Figure 4.

SNAREs implicated in autophagosome formation and maturation. Mammalian (top) and yeast (bottom) SNAREs involved in autophagy. All SNARES have a single transmembrane spanning domain except syntaxin 17, which has two transmembrane domains (Itakura et al. 2012).

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