Conditional knockdown of hMRS2 results in loss of mitochondrial Mg(2+) uptake and cell death

J Cell Mol Med. 2009 Apr;13(4):693-700. doi: 10.1111/j.1582-4934.2008.00328.x. Epub 2008 Mar 31.


The human gene MRS2L encodes a mitochondrial protein distantly related to CorA Mg(2+) transport proteins. Constitutive shRNA-mediated knockdown of hMRS2 in human HEK-293 cell line was found here to cause death. To further study its role in Mg(2+) transport, we have established stable cell lines with conditionally expressing shRNAs directed against hMRS2L. The cells expressing shRNA for several generations exhibited lower steady-state levels of free mitochondrial Mg(2+) ([Mg(2+)](m)) and reduced capacity of mitochondrial Mg(2+) uptake than control cells. Long-term expression of shRNAs resulted in loss of mitochondrial respiratory complex I, decreased mitochondrial membrane potential and cell death. We conclude that hMrs2 is the major transport protein for Mg (+) uptake into mitochondria and that expression of hMrs2 is essential for the maintenance of respiratory complex I and cell viability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cation Transport Proteins / metabolism*
  • Cell Death
  • Cell Line
  • Down-Regulation
  • Gene Knockdown Techniques*
  • Humans
  • Magnesium / metabolism*
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / metabolism*
  • RNA, Small Interfering / metabolism
  • Transfection


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