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Effect of cytosolic Mg2+ on mitochondrial Ca2+ signaling

Gergo Szanda1, Anikó Rajki, Sonia Gallego-Sandín

  • 1Department of Physiology, Faculty of Medicine, Semmelweis University, P.O. Box 259, 1444, Budapest, Hungary.

Pflugers Archiv : European Journal of Physiology
|July 17, 2008
PubMed

Insights

Magnesium (Mg2+) signals in cells can inhibit mitochondrial calcium (Ca2+) uptake. This finding reveals a new regulatory mechanism for cellular Ca2+ handling and mitochondrial function.

Area of Science:

  • Cellular biology
  • Mitochondrial function
  • Ion signaling

Background:

  • Cytosolic calcium (Ca2+) signals are critical for cellular processes and are followed by mitochondrial Ca2+ uptake.
  • Magnesium (Mg2+) is known to inhibit Ca2+ uptake in isolated mitochondria, but its role in intact cells is unclear.

Purpose of the Study:

  • To investigate the significance of Mg2+ in regulating mitochondrial Ca2+ uptake in intact cells.
  • To elucidate the relationship between cytosolic Ca2+ and Mg2+ signals.

Main Methods:

  • HEK293T cells were stimulated with extracellular ATP to activate purinergic receptors.
  • Cytosolic Ca2+ and Mg2+ concentrations ([Ca2+]c and [Mg2+]c) were measured.
  • Experiments involved manipulating extracellular bivalent cations, using uncaged Ca2+, and employing permeabilized cells with inositol 1,4,5-trisphosphate.

Main Results:

  • Extracellular ATP triggered parallel cytosolic Ca2+ and Mg2+ signals in HEK293T cells.
  • The Mg2+ signal was distinct from Ca2+ displacement of Mg2+ from binding sites.
  • Increased [Mg2+]c, within the physiological range observed, inhibited mitochondrial Ca2+ uptake in permeabilized cells.

Conclusions:

  • Cytosolic Mg2+ signals, generated by Ca2+-mobilizing agonists, can attenuate mitochondrial Ca2+ uptake.
  • This Mg2+-dependent inhibition represents a novel regulatory mechanism for mitochondrial Ca2+ handling in intact cells.

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