The mitochondrial calcium uniporter is a highly selective ion channel

Nature. 2004 Jan 22;427(6972):360-4. doi: 10.1038/nature02246.


During intracellular Ca2+ signalling mitochondria accumulate significant amounts of Ca2+ from the cytosol. Mitochondrial Ca2+ uptake controls the rate of energy production, shapes the amplitude and spatio-temporal patterns of intracellular Ca2+ signals, and is instrumental to cell death. This Ca2+ uptake is undertaken by the mitochondrial Ca2+ uniporter (MCU) located in the organelle's inner membrane. The uniporter passes Ca2+ down the electrochemical gradient maintained across this membrane without direct coupling to ATP hydrolysis or transport of other ions. Carriers are characterized by turnover numbers that are typically 1,000-fold lower than ion channels, and until now it has been unclear whether the MCU is a carrier or a channel. By patch-clamping the inner mitochondrial membrane, we identified a previously unknown Ca2+-selective ion channel sensitive to inhibitors of mitochondrial Ca2+ uptake. Our data indicate that this unique channel binds Ca2+ with extremely high affinity (dissociation constant < or =2 nM), enabling high Ca2+ selectivity despite relatively low cytoplasmic Ca2+ concentrations. The channel is inwardly rectifying, making it especially effective for Ca2+ uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • COS Cells
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels / metabolism*
  • Calcium Signaling / drug effects
  • Calcium-Binding Proteins / metabolism*
  • Cations, Divalent / metabolism
  • Cations, Divalent / pharmacology
  • Chlorocebus aethiops
  • Electric Conductivity
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism
  • Ion Channel Gating* / drug effects
  • Ion Transport / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Patch-Clamp Techniques
  • Ruthenium Compounds / pharmacology


  • Calcium Channels
  • Calcium-Binding Proteins
  • Cations, Divalent
  • Mitochondrial Proteins
  • Ru 360
  • Ruthenium Compounds
  • mitochondrial calcium uniporter
  • Adenosine Triphosphate
  • Calcium