SUMMARY PARAGRAPH for ATG29
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 7). 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 (8, 9, reviewed in 10). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 11). 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 (12, 13).
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 (14, 15). 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 (16 and reviewed in 11).
Atg29p is an autophagy-specific protein that localizes to the PAS and functions in PAS localization of other Atg proteins during nutrient stress (1, 4). atg29 null mutant cells show reduced viability in starvation conditions and severe defects in autophagy (the severity of the defect varies according to genetic background), but are normal for Cvt pathway function (1).
Atg29p interacts with Atg17p (apparently via coiled-coil domains in each protein), and localization of Atg29p, Atg17p, and Cis1p to the PAS is interdependent (4). These 3 autophagy-specific proteins and the Atg1p-Atg13p kinase complex are all required for PAS recruitment of other ATG proteins; thus it is proposed that Atg29p, Atg17p, and Cis1p form a complex that functions cooperatively with the Atg1p-Atg13p kinase complex to organize the PAS (4).
Proteins with similarity to Atg29p have been found in some other yeast species and filamentous fungi, but not in C. albicans, S. pombe, or higher eukaryotes, indicating Atg29p is not widely conserved (3).
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 (6 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 (6). 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 (3, 17).
Last updated: 2008-02-08