ABSTRACT
Introduction Normal cell growth and homeostasis requires balanced protein synthesis and degradation.
Yeast cells harbor two major systems for degradation of proteins, the proteasome and the vacu ole. While the proteasome is a large multi-protein particle predominantly breaking down poly-ubiquitin tagged proteins in the cytosol and nucleus, the vacuole is a complex membra nous compartment with several functions in addition to protein degradation. Within an acidic lumen favoring hydrolysis is an arsenal of enzymes capable of hydrolyzing all cellular macro molecules, not only proteins. The delimiting membrane of the vacuole contains a number of membrane transporters mediating the recirculation of hydrolyzed monomers such as amino acids and sugars back into the cytosol, a large protein complex that maintains the acidic inte rior by actively transporting protons across the membrane, as well as permeases facilitating transport of metal and other ions into the vacuole. Through these various transport processes the vacuole also serves a purpose in osmoregulation, in detoxifying the cytosol of elevated levels of harmful compounds, maintaining cytosolic pH and calcium levels, and in storage of me tabolites. The vacuolar membrane also contains a num ber o f trans-m em brane and membrane-associated proteins that regulate the targeting of vesicles destined for fusion with the vacuole. These vesicles may be endosomes or autophagosomes, and hence carriers of mac romolecules and organelles destined to be degraded, or they may be biosynthetic vesicles contain ing newly synthesized membrane proteins and lumenal vacuolar hydrolases delivered to maintain the vacuolar compartment during homeostasis or for expansion during cell proliferation.
