| Autophagy is the major degradative process for recycling cytoplasmic constituents and eliminating unnecessary organelles in eukaryotic cells. In yeast autophagy is primarily a response to nutrient limitation for maintaining cellular homeostasis, and in higher eukaryotes it also plays a role in developmental processes and various pathophysiological states. Due to its essentially unlimited degradative capacity, it is critical that regulatory mechanisms are in place to modulate the timing and magnitude of the autophagic response. One set of autophagy-related (Atg) proteins that seems to function in this regard includes a complex that contains the Atg1 kinase. Aside from Atg1, the proteins in this complex participate primarily in either nonspecific autophagy or specific types of autophagy, including the cytoplasm to vacuole targeting (Cvt) pathway, which operates under vegetative conditions, and peroxisome degradation. Accordingly, these proteins are prime candidates for factors that regulate the conversion between these pathways, including the change in size of the sequestering vesicle, the most obvious morphological difference.;Atg17 is identified as an autophagy-specific component based on a study of the atg17Delta mutant. It may regulate the magnitude of the autophagic response as part of the Atg1 complex.;Particularly, a physiological function of Atg17 is proposed to be the regulation of the initial steps of vesicle formation in starvation conditions. Most Atg proteins are recruited to the phagophore assembly site (PAS), a proposed site for vesicle formation during either nonspecific or specific types of autophagy. Therefore, appropriate recruitment of Atg proteins to this site is critical for their function in autophagy. Atg11 facilitates PAS recruitment for the Cvt pathway that occurs under vegetative conditions. In contrast, Atg17 seems to play a similar role to Atg11 in PAS formation under autophagy-inducing conditions. Furthermore I propose that protein complexes containing the Atg1 kinase have two roles for PAS formation during nonspecific autophagy. The Atg1 C terminus mediates an interaction with Atg13 and Atg17, facilitating a structural role of Atg1 that is needed to efficiently organize an initial step of PAS assembly, whereas Atg1 kinase activity affects the dynamics of protein movement at the PAS involved in Atg protein cycling. |
