Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 3, pp 375–396 | Cite as

Mitochondria and Ca2+ signaling: old guests, new functions

  • Wolfgang F. GraierEmail author
  • Maud Frieden
  • Roland Malli
Invited Review


Mitochondria are ancient endosymbiotic guests that joined the cells in the evolution of complex life. While the unique ability of mitochondria to produce adenosine triphosphate (ATP) and their contribution to cellular nutrition metabolism received condign attention, our understanding of the organelle’s contribution to Ca2+ homeostasis was restricted to serve as passive Ca2+ sinks that accumulate Ca2+ along the organelle’s negative membrane potential. This paradigm has changed radically. Nowadays, mitochondria are known to respond to environmental Ca2+ and to contribute actively to the regulation of spatial and temporal patterns of intracellular Ca2+ signaling. Accordingly, mitochondria contribute to many signal transduction pathways and are actively involved in the maintenance of capacitative Ca2+ entry, the accomplishment of Ca2+ refilling of the endoplasmic reticulum and Ca2+-dependent protein folding. Mitochondrial Ca2+ homeostasis is complex and regulated by numerous, so far, genetically unidentified Ca2+ channels, pumps and exchangers that concertedly accomplish the organelle’s Ca2+ demand. Notably, mitochondrial Ca2+ homeostasis and functions are crucially influenced by the organelle’s structural organization and motility that, in turn, is controlled by matrix/cytosolic Ca2+. This review intends to provide a condensed overview on the molecular mechanisms of mitochondrial Ca2+ homeostasis (uptake, buffering and storage, extrusion), its modulation by other ions, kinases and small molecules, and its contribution to cellular processes as fundamental basis for the organelle’s contribution to signaling pathways. Hence, emphasis is given to the structure-to-function and mobility-to-function relationship of the mitochondria and, thereby, bridging our most recent knowledge on mitochondria with the best-established mitochondrial function: metabolism and ATP production.


Mitochondrial Ca2+ Mitochondrial Ca2+ uniporter Mitochondrial ion transporters ROS Store operated Ca2+ entry Uncoupling proteins ER refilling Mitochondrial structure 



The scientific work of the authors is supported by the Austrian Funds (P16860-B09 and SFB F3010-B05; WFG), the Franz Lanyar Foundation (WFG), the Swiss National Science Foundation (#320000-107622; MF), and the Foundation Carlos and Elsie de Reuter (MF).


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Wolfgang F. Graier
    • 1
    Email author
  • Maud Frieden
    • 2
  • Roland Malli
    • 1
  1. 1.Molecular and Cellular Physiology Research Unit, MCPRU, Institute of Molecular Biology and Biochemistry, Center of Molecular MedicineMedical University of GrazGrazAustria
  2. 2.Department of Cell Physiology and MetabolismGeneva Medical CenterGeneva 4Switzerland

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