SCaMC-1 promotes cancer cell survival by desensitizing mitochondrial permeability transition via ATP/ADP-mediated matrix Ca(2+) buffering

Cell Death Differ. 2012 Apr;19(4):650-60. doi: 10.1038/cdd.2011.139. Epub 2011 Oct 21.


Ca(2+)-mediated mitochondrial permeability transition (mPT) is the final common pathway of stress-induced cell death in many major pathologies, but its regulation in intact cells is poorly understood. Here we report that the mitochondrial carrier SCaMC-1/SLC25A24 mediates ATP-Mg(2-)/Pi(2-) and/or HADP(2-)/Pi(2-) uptake into the mitochondria after an increase in cytosolic [Ca(2+)]. ATP and ADP contribute to Ca(2+) buffering in the mitochondrial matrix, resulting in desensitization of the mPT. Comprehensive gene expression analysis showed that SCaMC-1 overexpression is a general feature of transformed and cancer cells. Knockdown of the transporter led to vast reduction of mitochondrial Ca(2+) buffering capacity and sensitized cells to mPT-mediated necrotic death triggered by oxidative stress and Ca(2+) overload. These findings revealed that SCaMC-1 exerts a negative feedback control between cellular Ca(2+) overload and mPT-dependent cell death, suggesting that the carrier might represent a novel target for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / genetics
  • Adenosine Diphosphate / metabolism*
  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism*
  • Animals
  • COS Cells
  • Calcium / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Survival
  • Chlorocebus aethiops
  • Mice
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Necrosis
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Oxidative Stress / genetics
  • Permeability


  • Calcium-Binding Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Calcium