Mitochondrial free [Ca2+] increases during ATP/ADP antiport and ADP phosphorylation: exploration of mechanisms

Johan Haumann1, Ranjan K Dash, David F Stowe

  • 1Anesthesiology Research Laboratories, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Biophysical Journal
|August 18, 2010
PubMed

Insights

Mitochondrial calcium levels ([Ca2+](m)) increase with ADP influx and phosphorylation, influenced by matrix components. This process is linked to mitochondrial bioenergetics and calcium buffering within the matrix.

Area of Science:

  • Mitochondrial Physiology
  • Cellular Bioenergetics
  • Calcium Signaling

Background:

  • Mitochondrial calcium ([Ca2+](m)) dynamics are crucial for cellular energy production.
  • The precise mechanisms by which ADP influences [Ca2+](m) and bioenergetics remain incompletely understood.

Purpose of the Study:

  • To investigate the impact of ADP influx and phosphorylation on mitochondrial free calcium ([Ca2+](m)).
  • To elucidate the roles of phosphate (P(i)), magnesium (Mg2+), calcium uniporter activity, and bioenergetic state in modulating [Ca2+](m).

Main Methods:

  • Measurements of [Ca2+](m), membrane potential, redox state, matrix volume, pH(m), and O2 consumption in guinea pig heart mitochondria.
  • Experiments conducted with varying concentrations of Mg2+ and P(i), and in the presence of ruthenium red, carboxyatractyloside, or oligomycin.

Main Results:

  • Energized mitochondria exhibited a dose-dependent increase in [Ca2+](m) upon CaCl2 addition, attenuated by higher Mg2+.
  • ADP addition transiently elevated [Ca2+](m) up to twofold, partially due to matrix contraction.
  • Oligomycin reduced the ADP-induced [Ca2+](m) increase, while carboxyatractyloside prevented it.
  • CaCl2 addition had minimal impact on mitochondrial bioenergetics.

Conclusions:

  • Matrix ADP influx and subsequent phosphorylation significantly increase [Ca2+](m).
  • This increase is primarily attributed to the interaction of matrix Ca2+ with ATP, ADP, P(i), and buffering proteins.
  • Mitochondrial calcium regulation is complex and influenced by matrix composition and bioenergetic status.

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