Interrelation Between Protein Synthesis, Proteostasis and Life Span

Abstract: The production of newly synthesized proteins is a key process of protein homeostasis that initiates the biosyn-thetic flux of proteins and thereby determines the composition, stability and functionality of the proteome. Protein synthe-sis is highly regulated on multiple levels to adapt the proteome to environmental and physiological challenges such as ag-ing and proteotoxic conditions. Imbalances of protein folding conditions are sensed by the cell that then trigger a cascade of signaling pathways aiming to restore the protein folding equilibrium. One regulatory node to rebalance proteostasis upon stress is the control of protein synthesis itself. Translation is reduced as an immediate response to perturbations of the protein folding equilibrium that can be observed in the cytosol as well as in the organelles such as the endoplasmatic reticulum and mitochondria. As reduction of protein synthesis is linked to life span increase, the signaling pathways regu-lating protein synthesis might be putative targets for treatments of age-related diseases. Eukaryotic cells have evolved a complex system for protein synthesis regulation and this review will summarize cellular strategies to regulate mRNA translation upon stress and its impact on longevity