SUMMARY PARAGRAPH for ATG17
Autophagy is a highly conserved eukaryotic pathway for sequestering and transporting bulk cytoplasm, including proteins and organelle material, to the lysosome for degradation (reviewed in 8). Upon starvation for nutrients such as carbon, nitrogen, sulfur, and various amino acids, or upon endoplasmic reticulum stress, cells initiate formation of a double-membrane vesicle, termed an autophagosome, that mediates this process (9, 10, reviewed in 11). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 12). Null mutations in most of these genes prevent induction of autophagy, and cells do not survive nutrient starvation; however, these mutants are viable in rich medium. Some of the Atg proteins are also involved in a constitutive biosynthetic process termed the cytoplasm-to-vacuole targeting (Cvt) pathway, which uses autophagosomal-like vesicles for selective transport of hydrolases aminopeptidase I (Lap4p) and alpha-mannosidase (Ams1p) to the vacuole (13, 14).
Autophagy proceeds via a multistep pathway (a summary diagram (download pdf) kindly provided by Dan Klionsky). First, nutrient availability is sensed by the TORC1 complex and also cooperatively by protein kinase A and Sch9p (15, 16). Second, signals generated by the sensors are transmitted to the autophagosome-generating machinery comprised of the 17 Atg gene products. These 17 proteins collectively form the pre-autophagosomal structure/phagophore assembly site (PAS). The PAS generates an isolation membrane (IM), which expands and eventually fuses along the edges to complete autophagosome formation. At the vacuole the outer membrane of the autophagosome fuses with the vacuolar membrane and autophagic bodies are released, disintegrated, and their contents degraded for reuse in biosynthesis (17 and reviewed in 12).
Atg17p is an autophagy-specific protein that acts as a scaffold for the other ATG proteins during PAS organization (6, 18). Atg17p has many interaction partners and may form complexes with proteins such as Atg20p, Snx4p, Atg29p, Cis1p, and Atg11p to localize other factors to the PAS (19, 18, 14). Efficient localization of Atg17p to the PAS is itself dependent on the EPS15 homology domain proteins Irs4p and Tax4p (20).
Atg17p, along with Atg13p, is also a regulatory subunit of the Atg1p protein kinase complex and is required for vesicle expansion during autophagy (5, 4, reviewed in 12). Atg13p and Atg17p stimulate Atg1p kinase activity and formation of this complex is specific to autophagy and enhanced during starvation (4).
atg17 mutants are defective in autophagy, blocked in pexophagy, have lengthened telomeres, and cannot survive under starvation conditions (5, 21, 4). Autophagosomes in atg17 null mutants are fewer in number and less than half the normal size (5, 4). Overexpression of ATG17 inhibits filamentous growth (22). ATG17 homologs have been identified in all yeast species and most filamentous fungi studied to date, but no ATG17 ortholog has yet been identified in higher eukaryotes (23).
about autophagy nomenclature
The initial identification of factors involved in autophagy was carried out by several independent labs, which led to a proliferation of nomenclature for the genes and gene products involved. The differing gene name acronyms from these groups included APG, AUT, CVT, GSA, PAG, PAZ, and PDD (1 and references therein). A concerted effort was made in 2003 by the scientists working in the field to unify the nomenclature for these genes, and "AuTophaGy-related" genes are now denoted by the letters ATG (1). In addition to the ATG gene names that have been assigned to S. cerevisiae proteins and their orthologs, several ATG gene names, including ATG25, ATG28, and ATG30, have been used to designate proteins in other ascomycete yeast species for which there is no identifiable equivalent in S. cerevisiae (23, 24).
Last updated: 2008-02-08