Hindawi Publishing Corporation International Journal of Cell Biology Volume 2010, Article ID 214074, 23 pages doi:10.1155/2010/214074 Review Article Cellular Stress Responses: Cell Survival and Cell Death Simone Fulda, 1 Adrienne M. Gorman, 2 Osamu Hori, 3 and Afshin Samali 2 1 Children’s Hospital, Ulm University, Eythstraße. 24, 89075 Ulm, Germany 2 School of Natural Sciences, National University of Ireland, Galway, University Road, Galway, Ireland 3 Kanazawa University Graduate School of Medical Science, Department of Neuroanatomy, Kanazawa City, Ishikawa, 920-8640 Japan, Japan Correspondence should be addressed to Simone Fulda, simone.fulda@uniklinik-ulm.de Received 4 August 2009; Accepted 20 November 2009 Academic Editor: Srinivasa M. Srinivasula Copyright © 2010 Simone Fulda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective or destructive stress response depends to a large extent on the nature and duration of the stress as well as the cell type. Also, there is often the interplay between these responses that ultimately determines the fate of the stressed cell. The mechanism by which a cell dies (i.e., apoptosis, necrosis, pyroptosis, or autophagic cell death) depends on various exogenous factors as well as the cell’s ability to handle the stress to which it is exposed. The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson’s disease, myocardial infarction, and cancer. 1. Overview of Cellular Stress Responses Cells respond to stress in a variety of ways ranging from activation of pathways that promote survival to eliciting programmed cell death that eliminates damaged cells. The cell’s initial response to a stressful stimulus is geared towards helping the cell to defend against and recover from the insult. However, if the noxious stimulus is unresolved, then cells activate death signaling pathways. The fact that the cell’s survival critically depends on the ability to mount an appro- priate response towards environmental or intracellular stress stimuli can explain why this reaction is highly conserved in evolution. For example, antioxidant defence mechanisms against oxidative injury and stress proteins such as heat shock proteins occur in lower organisms as well as the mammals. There are many different types of stress and the response a cell mounts to deal with these conditions will depend on the type and level of the insult. For example, protective responses such as the heat shock response or the unfolded protein response mediate an increase in chaperone protein activity which enhances the protein folding capacity of the cell, thus counteracting the stress and promoting cell survival. The adaptive capacity of a cell ultimately determines its fate. Therefore, depending on the level and mode of stress, different defense mechanisms and prosurvival strategies are mounted; however, if these are unsuccessful, then the cell death programs are activated to eliminate these damaged cells from the organism. The mechanism by which a cell dies, that is, apoptosis, necrosis, pyroptosis, or autophagic cell death, often depends on its ability to cope with the conditions to which it is exposed. In this review we initially discuss the different forms of cell death that can be activated by adaptive responses because activation of death signaling pathways is the ultimate response to all types of persistent irresolvable stress. In Section 3 we will discuss the many types of stress a cell can encounter and the different responses that are activated to survive adverse conditions. Finally, we will discuss the involvement or contribution of cellular stress responses to disease states. 2. Stress-Induced Cell Death Cell death has many forms and shapes. Cell death research encompasses not only the study of programmed forms of cell death (both apoptosis and autophagic cell death), necrosis and other modes of cellular demise but also the role these