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Caspase-12 and ER-Stress-Mediated Apoptosis

The Story So Far

Authors

  • EVA SZEGEZDI,

    1. Cell Stress and Apoptosis Research Group, Department of Biochemistry, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • UNA FITZGERALD,

    1. Cell Stress and Apoptosis Research Group, Department of Biochemistry, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • AFSHIN SAMALI

    Corresponding author
    1. Cell Stress and Apoptosis Research Group, Department of Biochemistry, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
    • Address for correspondence: Afshin Samali, Cell Stress and Apoptosis Research Group, Department of Biochemistry, NUI, Galway, Ireland. Voice: +353-91-750393; fax: +353-91-512504. afshin.samali@nuigalway.ie

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Abstract

Abstract: The labyrinth of the endoplasmic reticulum (ER) interweaves the cytosol and connects to the nucleus, mitochondria, and the plasma membrane. In the lumen of the ER, the essential function of lipid synthesis, Ca2+ storage, folding, and maturation of proteins take place. Therefore, the tight regulation and maintenance of ER homeostasis is vital. Disturbance of the Ca2+ homeostasis during hypoxia, or imbalance between the demand and capacity of the protein-folding apparatus, initiates an adaptive response of the cell, termed the unfolded protein response (UPR, ER stress response). As a result, ER-localized chaperones are induced, protein synthesis is slowed down, and a protein degrading system is initiated. However, if the ER stress cannot be alleviated, it culminates in apoptosis. This paper reviews the newly outlined signaling pathways of the unfolded protein response and describes the central role of caspase-12 in the initiation of cell death. The complex role of the ER and its signaling pathways provides a novel angle on apoptosis research and may offer a key to apoptosis-associated diseases.

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