Stress response

Stress in the sense of a disruption to the normal environs of a cell or organ or organism is a real problem. Knowledge of how the body reacts is mostly confined to hormone reaction, the flight and fight hormones etc.
There are a fascinating series of papers in Nature 5th Feb 2009 on the cellular response to stress, this will include nutrient deprivation.
In cells, protein homeostasis, which is a delicate balance between maintaining protein conformations, refolding misfolded proteins and degrading damaged proteins, is normally maintained by regulatory networks that control protein synthesis and degradation.
Molecular chaperones are key players in protein homeostasis, helping proteins to fold and preventing aggregation of misfolded proteins, which could have substantial, disease-related consequences. When environmental stress such as nutrient deprivation or oxygen shortage disrupts protein homeostasis, the cell responds. Nowhere is this process more controlled than in the endoplasmic reticulum, an extensive organelle consisting of inter connecting tubules that serves as the synthesis site for secretory and membrane proteins. Nicchitta, Korennykh et al. and Aragon et al demonstrate how that stress elicits the assembly at the endoplasmic reticulum of signalling centres that sense the accumulation of unfolded proteins.
They have looked at the emergency response at the endoplasmic reticulum.
In the unstressed cell, protein folding within the endoplasmic reticulum occurs efficiently; the unfolded protein sensor and signalling protein Irelp is inactive, and the HACl messenger RNA remains untranslated in the cytoplasm.
Under stress, protein folding is disrupted and unfolded proteins accumulate in the endoplasmic reticulum. It emerges that the binding of unfolded proteins to Irelp promotes clustering of this protein and activation of the endonuclease activity of its cytosolic domain. HAC1 mRNAs, themselves attached to multiple ribosomes, are then recruited to the activated Irelp clusters, and are processed there, allowing translation of the essential stress-response factor Hac1 p protein.
Nicchitta 2009 How to combat stress Nature vol 457 pp668-9
Korennykh et al 2009 The unfolded protein response signals through the high order assembly of Ire1 Nature vol 457, 687-693
Aragon et al 2009 Messenger RNA targeting to endoplasmic reticulum stress signalling sites Nature vol 457 pp 736-740

Martin Eastwood
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