Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and vulnerability to stress

Sci Rep. 2016 Jul 26;6:30027. doi: 10.1038/srep30027.


Cellular energy production processes are composed of many Mg(2+) dependent enzymatic reactions. In fact, dysregulation of Mg(2+) homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg(2+) stores. Several biological stimuli alter mitochondrial Mg(2+) concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg(2+) alteration affect cellular energy metabolism remains unclear. Mg(2+) transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg(2+) uptake system. Here, we comprehensively analyzed intracellular Mg(2+) levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg(2+) homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg(2+) via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg(2+) level in response to physiological stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / genetics
  • Cation Transport Proteins / genetics*
  • Cell Line, Tumor
  • Cell Physiological Phenomena
  • Energy Metabolism / physiology*
  • HeLa Cells
  • Homeostasis / physiology
  • Humans
  • Magnesium / metabolism*
  • Membrane Potential, Mitochondrial / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Stress, Physiological / genetics*


  • Cation Transport Proteins
  • MRS2 protein, human
  • Mitochondrial Proteins
  • RNA, Small Interfering
  • Magnesium