Journal of Bioenergetics and Biomembranes

, Volume 32, Issue 1, pp 35–46

Mitochondria in Ca2+ Signaling and Apoptosis

  • Soraya S. Smaili
  • Yi-Te Hsu
  • Richard J. Youle
  • James T. Russell
Article

DOI: 10.1023/A:1005508311495

Cite this article as:
Smaili, S.S., Hsu, YT., Youle, R.J. et al. J Bioenerg Biomembr (2000) 32: 35. doi:10.1023/A:1005508311495

Abstract

Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injuryand programmed cell death; mitochondria play a pivotal role in the regulation of such cytosolicCa2+ ([Ca2+]c) signals. Mitochondria are endowed with multiple Ca2+ transport mechanismsby which they take up and release Ca2+ across their inner membrane. These transport processesfunction to regulate local and global [Ca2+]c, thereby regulating a number of Ca2+-sensitivecellular mechanisms. The permeability transition pore (PTP) forms the major Ca2+ effluxpathway from mitochondria. In addition, Ca2+ efflux from the mitochondrial matrix occursby the reversal of the uniporter and through the inner membrane Na+/Ca2+ exchanger. Duringcellular Ca2+ overload, mitochondria take up [Ca2+]c, which, in turn, induces opening of PTP,disruption of mitochondrial membrane potential (ΔΨm) and cell death. In apoptosis signaling,collapse of ΔΨ;m and cytochrome c release from mitochondria occur followed by activationof caspases, DNA fragmentation, and cell death. Translocation of Bax, an apoptotic signalingprotein from the cytosol to the mitochondrial membrane, is another step during thisapoptosis-signaling pathway. The role of permeability transition in the context of cell death in relationto Bcl-2 family of proteins is discussed.

Ca2+ signaling inositol 1,4,5-trisphosphate receptor mitochondrial Ca2+ uptake mitochondrial Ca2+ efflux permeability transition apoptosis Bcl-2 family 

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Soraya S. Smaili
    • 1
    • 2
  • Yi-Te Hsu
    • 3
  • Richard J. Youle
    • 3
  • James T. Russell
    • 1
    • 4
  1. 1.Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA
  2. 2.Departmento de farmacologiaUniversidade Federal de Säo Paulo (UNIFESP)Säo PauloBrazil
  3. 3.Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaUSA
  4. 4.Departmento de farmacologiaUniversidade Federal de Säo Paulo (UNIFESP)Säo PauloBrazil