Heat shock response

The heat shock response (HSR) is a cell stress response that increases the number of molecular chaperones to combat the negative effects on proteins caused by stressors such as increased temperatures, oxidative stress, and heavy metals.[1] In a normal cell, proteostasis (protein homeostasis) must be maintained because proteins are the main functional units of the cell.[2] Many proteins take on a defined configuration in a process known as protein folding in order to perform their biological functions. If these structures are altered, critical processes could be affected, leading to cell damage or death.[3] The heat shock response can be employed under stress to induce the expression of heat shock proteins (HSP), many of which are molecular chaperones, that help prevent or reverse protein misfolding and provide an environment for proper folding.[4]

Protein folding is already challenging due to the crowded intracellular space where aberrant interactions can arise; it becomes more difficult when environmental stressors can denature proteins and cause even more non-native folding to occur.[5] If the work by molecular chaperones is not enough to prevent incorrect folding, the protein may be degraded by the proteasome or autophagy to remove any potentially toxic aggregates.[6] Misfolded proteins, if left unchecked, can lead to aggregation that prevents the protein from moving into its proper conformation and eventually leads to plaque formation, which may be seen in various diseases.[7] Heat shock proteins induced by the HSR can help prevent protein aggregation that is associated with common neurodegenerative diseases such as Alzheimer's, Huntington's, or Parkinson's disease.[8]

The diagram depicts actions taken when a stress is introduced to the cell. Stress will induce HSF-1 and cause proteins to misfold. Molecular chaperones will aid these proteins to fold correctly or if the degree of misfolding is too severe, the protein will be eliminated through the proteasome or autophagy.
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  3. ^ Richter K, Haslbeck M, Buchner J (October 2010). "The heat shock response: life on the verge of death". Molecular Cell. 40 (2): 253–66. doi:10.1016/j.molcel.2010.10.006. PMID 20965420.
  4. ^ Weibezahn J, Schlieker C, Tessarz P, Mogk A, Bukau B (August 2005). "Novel insights into the mechanism of chaperone-assisted protein disaggregation". Biological Chemistry. 386 (8): 739–44. doi:10.1515/BC.2005.086. PMID 16201868. S2CID 42852756.
  5. ^ Fink AL (April 1999). "Chaperone-mediated protein folding". Physiological Reviews. 79 (2): 425–49. doi:10.1152/physrev.1999.79.2.425. PMID 10221986.
  6. ^ Cuervo AM, Wong E (January 2014). "Chaperone-mediated autophagy: roles in disease and aging". Cell Research. 24 (1): 92–104. doi:10.1038/cr.2013.153. PMC 3879702. PMID 24281265.
  7. ^ Tower J (July 2009). "Hsps and aging". Trends in Endocrinology and Metabolism. 20 (5): 216–22. doi:10.1016/j.tem.2008.12.005. PMC 3835556. PMID 19394247.
  8. ^ Wyttenbach A, Arrigo AP (2013). The Role of Heat Shock Proteins during Neurodegeneration in Alzheimer's, Parkinson's and Huntington's Disease. Landes Bioscience.