# Chapter 8: Your cells are stressed too

Stress is a problem for many people nowadays because it can cause serious health problems and complications. However, stress affects not only the whole organism, but also individual cells. At the cellular level, stress can be defined as a set of biochemical reactions that are activated when internal or external conditions change. If the cell does not react correctly and quickly enough to these changes, it can even lead to death. Among the main factors that trigger stress in cells are mechanical damage (cell wall damage or damage of cytoplasmic membrane, pressure exerted on cells) and the action of biological (viruses), chemical (toxic substances, for example alcohol) or physical (UV radiation) agents.

In the study of cellular stress and cellular response, temperature stress has played a key role because it is easily induced in laboratory conditions. Temperature stress is generated by a change in the temperature of the environment, which can affect many intracellular processes. Optimal temperature is crucial to ensure the proteins fold correctly, i.e. achieve the correct conformation, to function properly. During folding, the parts of proteins called active domains, which are crucial for interaction with other proteins or with DNA, are located on the outer parts of protein to make them accessible for reactions. The correct conformation is ensured by chemical bonds and interactions between the functional groups of individual amino acids. However, these bonds are sensitive to changes in temperature, and as soon as there is an increase in temperature, they are disrupted. The disruption results in changes of protein conformation and this protein cannot perform its functions correctly. For example, transcription factors are proteins whose main function is to interact with DNA and regulate transcription. In order to be able to bind to DNA, they have DNA-binding domains in their structure. For proper folding of the transcription factor, the DNA-binding domains must be located on the surface where they can interact with target DNA sequence. However, if there is a change in conformation caused by, for example, temperature stress, these domains can be covered by another part of the protein, which prevents them from binding to DNA. Due to the incorrect conformation, the transcription factor is subsequently unable to fulfil its function and cell must quickly resolve the situation. There are two possible ways to deal with this situation. Either the cell marks the protein for degradation (by a ubiquitin molecule), or the cell can repair the damaged protein. For repair, special proteins called "heat shock" proteins (Hsp) or chaperones are used. Chaperons bind to the targeted damaged protein, break the wrong bonds and restore the original conformation of the protein. During the response to stress, cells preferentially use chaperones, because the degradation of a damaged protein and the synthesis of a new one is an energy-intensive process. However, such correction of protein conformation cannot take place in cells under all conditions. If the temperature in the cell is elevated for a long time or constantly rises, the chaperones themselves may be damaged, resulting in cell death. In addition, Hsp proteins are not only involved in the response to temperature stress, but also in the response to other agents, such as UV radiation or starvation. In cells, they have their physiological function even outside of stressful situations, for example, they have a role in the mutual interaction between proteins, in which they ensure the correct conformation and also prevent protein aggregation.