Solute carrier 41A3 encodes for a mitochondrial Mg(2+) efflux system

Sci Rep. 2016 Jun 15:6:27999. doi: 10.1038/srep27999.


The important role of magnesium (Mg(2+)) in normal cellular physiology requires flexible, yet tightly regulated, intracellular Mg(2+) homeostasis (IMH). However, only little is known about Mg(2+) transporters of subcellular compartments such as mitochondria, despite their obvious importance for the deposition and reposition of intracellular Mg(2+) pools. In particular, knowledge about mechanisms responsible for extrusion of Mg(2+) from mitochondria is lacking. Based on circumstantial evidence, two possible mechanisms of Mg(2+) release from mitochondria were predicted: (1) Mg(2+) efflux coupled to ATP translocation via the ATP-Mg/Pi carrier, and (2) Mg(2+) efflux via a H(+)/Mg(2+) exchanger. Regardless, the identity of the H(+)-coupled Mg(2+) efflux system is unknown. We demonstrate here that member A3 of solute carrier (SLC) family 41 is a mitochondrial Mg(2+) efflux system. Mitochondria of HEK293 cells overexpressing SLC41A3 exhibit a 60% increase in the extrusion of Mg(2+) compared with control cells. This efflux mechanism is Na(+)-dependent and temperature sensitive. Our data identify SLC41A3 as the first mammalian mitochondrial Mg(2+) efflux system, which greatly enhances our understanding of intracellular Mg(2+) homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Transport System y+L / genetics*
  • Amino Acid Transport System y+L / metabolism*
  • Cloning, Molecular
  • HEK293 Cells
  • Humans
  • Magnesium / metabolism*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Sodium / metabolism
  • Temperature


  • Amino Acid Transport System y+L
  • Mitochondrial Proteins
  • Neoplasm Proteins
  • SLC43A1 protein, human
  • Adenosine Triphosphate
  • Sodium
  • Magnesium