Interrelation Between Protein Synthesis, Proteostasis and Life Span
Kristin Arnsburg and Janine Kirstein-Miles
Pages 66-75 (10)
The production of newly synthesized proteins is a key process of protein homeostasis that initiates the biosynthetic
flux of proteins and thereby determines the composition, stability and functionality of the proteome. Protein synthesis
is highly regulated on multiple levels to adapt the proteome to environmental and physiological challenges such as aging
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 regulating
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.
Aging, Chaperone, Life span, mRNA Translation, Proteostasis, Stress response, UPR.
Leibniz-Institut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. Robert-Rossle- Straße 10; 13125 Berlin, Germany.