The role of SERCA2a/PLN complex, Ca2+ homeostasis, and anti-apoptotic proteins in determining cell fate

Elizabeth Vafiadaki, Vasiliki Papalouka, Demetrios A. Arvanitis, Evangelia G. Kranias, Despina Sanoudou

    Research output: Contribution to journalReview article

    28 Citations (Scopus)


    Intracellular calcium is a major coordinator of numerous aspects of cellular physiology, including muscle contractility and cell survival. In cardiac muscle, aberrant Ca2+ cycling has been implicated in a range of pathological conditions including cardiomyopathies and heart failure. The sarco(endo)plasmic reticulum Ca2+ transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca2+ homeostasis and, therefore, cardiac function. Herein, we discuss the mechanisms through which SERCA2a and PLN control cardiomyocyte function in health and disease. Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2. Recent evidence indicates that proteins of the Bcl-2 family can influence ER Ca 2+ content, a critical determinant of cellular sensitivity to apoptosis. The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca2+ homeostasis and cell survival, with significant therapeutic potential.

    Original languageEnglish
    Pages (from-to)687-700
    Number of pages14
    JournalPflugers Archiv European Journal of Physiology
    Issue number3
    Publication statusPublished - 1 Jan 2009



    • Apoptosis
    • Ca regulation
    • Calcium ATPase
    • Cardiac function
    • Mitochondria
    • Sarcoplasmic reticulum

    ASJC Scopus subject areas

    • Physiology
    • Clinical Biochemistry
    • Physiology (medical)

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