Protein Homeostasis and Cellular Quality Control

Three cellular machineries — translation, folding or as-sembly, and clearance — act coordinately to maintain the stability of the proteome and to ensure its continuous re-newal under normal conditions ( 1 – 4). When protein dam-age occurs, these cellular machineries triage to repair damage by either refolding — if possible — or degrading the damaged proteins to prevent the accumulation of these toxic products inside the cell. Consequently, protein homeostasis results from the coordinated action of the quality control systems and the systems that govern each of the different processes that proteins undergo inside cells, including syn-thesis, assembly or disassembly, traffi cking, and transloca-tion to different intracellular compartments. Altered protein handling has been implicated as a basis for a large number of common human diseases known a