Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway

Organelle biogenesis and turnover are necessary to maintain biochemical pro cesses that are appropriate to the needs of the eukaryotic cell. Specific d egradation of organelles in response to changing environmental cues is one aspect of achieving proper metabolic function. For example, the yeast Sacch aromyces cerevisiae adjusts the level of peroxisomes in response to differi ng nutritional sources. When cells are grown on oleic acid as the sole carb on source, peroxisome biogenesis is induced. Conversely, a subsequent shift to glucose-rich or nitrogen-limiting conditions results in peroxisome degr adation. The degradation process, pexophagy, requires the activity of vacuo lar hydrolases. In addition, peroxisome degradation is specific. Analyses o f cellular marker proteins indicate that peroxisome degradation under these conditions occurs more rapidly and to a greater extent than mitochondrial, Golgi, or cytosolic protein delivery to the vacuole by the non-selective a utophagy pathway. To elucidate the molecular mechanism of selective peroxis ome degradation, we examined pexophagy in mutants that are defective ill au tophagy (apg) and the selective targeting of aminopeptidase I to the vacuol e by the cytoplasm to vacuole targeting (Cvt) pathway. Inhibition of peroxi some degradation in cvt and apg mutants indicates that these pathways overl ap and that peroxisomes are delivered to the vacuole by a mechanism that ut ilizes protein components of the Cvt/autophagy pathways.