SUMMARY PARAGRAPH for ATG22
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 6). 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 (7, 8, reviewed in 9). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 10). 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 (2, 11).
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 (12, 13). 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 (14 and reviewed in 10).
ATG22 encodes a vacuolar integral membrane protein that functions as an amino acid efflux pump for leucine, a function necessary for cell viability during starvation (5). Atg22p efflux function is required at the last stages of autophagy, when autophagic body breakdown products are recycled to the cytosol (reviewed in 15). Atg22p is partially redundant in function with vacuolar efflux proteins Avt3p and Avt4p (5).
Earlier research suggested that the starved atg22 null mutant is defective in breakdown of autophagic bodies that have reached the vacuole (4). More recent evidence shows that breakdown occurs normally but is delayed (5). This delay is likely an indirect effect of the mutant defect in recycling amino acids that accumulate in the vacuole back into the cytosol upon autophagic body breakdown (5, reviewed in 16). Inappropriate accumulation of these amino acids is thought to affect expression of genes encoding proteins involved in autophagic body breakdown, leading to the apparent delay in breakdown (reviewed in 16).
ATG22 expression increases in response to nitrogen starvation (5). Proteins with varying degrees of similarity to Atg22p are found in most yeast species and filamentous fungi but not in higher eukaryotes (15).
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 (15, 17).
Last updated: 2008-02-08