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The Endoplasmic Reticulum Pathway

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Essentials of Apoptosis

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Abstract

Virtually all organisms adapt to stress in order to prolong their survival. At the subcellular level, the endoplasmic reticulum (ER) responds to stress by inducing ER-specific signaling pathways to reestablish homeostasis between protein synthesis and processing, a mechanism called the unfolded protein response (UPR). However, when cells endure a persistent irreversible state of ER stress, they undergo apoptosis. Apoptosis initiated at the ER is distinct from mitochondrial or death receptor-mediated apoptosis but may involve or require cross-talk from intrinsic or extrinsic pathways. Two functions of the ER are to facilitate the maturation of newly synthesized proteins and to maintain stores of intracellular calcium. Therefore, apoptosis induced by ER stress is frequently characterized by perturbations in protein processing and transport and/or a loss of calcium homeostasis. Additionally, because the ER and mitochondria reside in close proximity to one another, pro- and antiapoptotic proteins, such as the Bcl-2 family members, localize to the ER to regulate apoptosis in response to stress. This chapter summarizes the key pathways associated with cell survival and apoptotic cell death in the context of ER stress and aberrant calcium signaling.

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  1. Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, WRB 3-133, Cleveland, OH 44106-7285, USA

    Michael W. Harr & Clark W. Distelhorst

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    Harr, M.W., Distelhorst, C.W. (2009). The Endoplasmic Reticulum Pathway. In: Dong, Z., Yin, XM. (eds) Essentials of Apoptosis. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-381-7_7

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