Mitochondria respond to Ca2+ already in the submicromolar range: correlation with redox state

Cell Calcium. 2002 Feb;31(2):97-104. doi: 10.1054/ceca.2001.0264.


Rapid formation of high-Ca2+ perimitochondrial cytoplasmic microdomains has been shown to evoke mitochondrial Ca2+ signal and activate mitochondrial dehydrogenases, however, the significance of submicromolar cytoplasmic Ca2+ concentrations in the control of mitochondrial metabolism has not been sufficiently elucidated. Here we studied the mitochondrial response to application of Ca2+ at buffered concentrations in permeabilized rat adrenal glomerulosa cells, in an insulin-producing cell line (INS-1/EK-3) and in an osteosarcoma cell line (143BmA-13). Mitochondrial Ca2+ concentration was measured with the fluorescent dye rhod-2 and, using an in situ calibration method, with the mitochondrially targeted luminescent protein mt-aequorin. In both endocrine cell types, mitochondrial Ca2+ concentration increased in response to elevated cytoplasmic Ca2+ concentration (between 60 and 740 nM) and an increase in mitochondrial Ca2+ concentration could be revealed already at a cytoplasmic Ca2+ concentration step from 60-140 nM. Similar responses were observed in the osteosarcoma cell line, although a clearcut response was first observed at 280 nM extramitochondrial Ca2+ only. As examined in glomerulosa cells, graded increases in cytoplasmic Ca2+ concentration were associated with graded increases in the reduction of mitochondrial pyridine nucleotides, consistent with Ca2+-dependent activation of mitochondrial dehydrogenases. Our data indicate that in addition to the recognized role of high-Ca2+ cytoplasmic microdomains, also small Ca2+ signals may influence mitochondrial metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aequorin
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling
  • Cell Line
  • Fluorescent Dyes
  • Heterocyclic Compounds, 3-Ring
  • Male
  • Mitochondria / metabolism*
  • NADP / metabolism
  • Oxidation-Reduction
  • Rats
  • Rats, Wistar
  • Tumor Cells, Cultured
  • Zona Glomerulosa / cytology
  • Zona Glomerulosa / metabolism


  • Fluorescent Dyes
  • Heterocyclic Compounds, 3-Ring
  • rhod-2
  • Aequorin
  • NADP
  • Calcium