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Formation and maturation of the autophagosome
Author(s) -
Mizushima Noboru
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.99.2
Subject(s) - autophagy , autophagosome , microbiology and biotechnology , lysosome , atg16l1 , cytoplasm , biology , bag3 , lipid bilayer fusion , chemistry , phagosome , intracellular , biochemistry , membrane , apoptosis , enzyme
Autophagy is one of the major degradation pathways in the cell. In autophagy, intracellular components are sequestered by autophagosomes and then degraded upon fusion with lysosomes. Formation of the autophagosome is governed by organized functions of autophagy‐related (Atg) proteins, which were originally identified in yeast. We showed that the Atg hierarchy is well conserved in other eukaryotes including mammals. We also investigated the recognition mechanism of selective autophagy substrates and found that p62 and depolarized mitochondria, and ferritin can localize to the ER‐associated autophagosome formation site, independently of Atg proteins. These observations suggest that there is a common mechanism that recruits autophagy substrates to the autophagosome formation site, which is independent of binding to the autophagosomal membrane. Another important question that remains to be solved is how the autophagosome can specifically fuse with the lysosome. If the lysosome fuses with the elongating isolation membrane (unclosed autophagosome), it cannot accomplish degradation of cytoplasmic materials. We recently identified an autophagosomal SNARE, which is absent in the isolation membrane. Thus, the late recruitment of the SNARE to the autophagosome can prevent premature fusion with the lysosome.