Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 3, pp 687–700

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
Cardiovascular Physiology


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 Ca2+ 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.


Ca2+ regulation Sarcoplasmic reticulum Mitochondria Cardiac function Calcium ATPase Apoptosis 


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Elizabeth Vafiadaki
    • 1
  • Vasiliki Papalouka
    • 1
  • Demetrios A. Arvanitis
    • 1
  • Evangelia G. Kranias
    • 1
    • 2
  • Despina Sanoudou
    • 1
  1. 1.Molecular Biology DivisionBiomedical Research Foundation, Academy of AthensAthensGreece
  2. 2.Department of Pharmacology and Cell Biophysics, College of MedicineUniversity of CincinnatiCincinnatiUSA

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