Like the ALR genes, the MRS2 gene was cloned and sequenced before it was identified as a Mg²⁺ transporter.
The MRS2 gene was identified in the nuclear genome of yeast in a screen for suppressors of a mitochondrial gene RNA splicing mutation, and was cloned and sequenced by Wiesenberger et al. (
1992).
Mrs2p was not identified as a putative Mg²⁺ transporter until Bui et al. (
1999).
Gregan et al. (
2001a) identified LPE10 by homology to MRS2 and showed that both LPE10 and MRS2 mutants altered the Mg²⁺ content of yeast mitochondria and affected RNA splicing activity in the organelle.
Mg²⁺ transport has been shown to be directly mediated by Mrs2p, but not for Lpe10p.

The Mrs2p and Lpe10p proteins are 470 and 413 amino acid residues in size, respectively, and a 250–300 amino acid region in the middle of the proteins shows a weak similarity to the full CorA protein.
The TM topologies of the Mrs2p and Lpe10p proteins have been assessed using a protease protection assay and are shown in the figure.
TM 1 and 2 correspond to TM 2 and 3 in the CorA protein.
The conserved GMN motif is at the outside end of the first TM domain, and when the glycine (G) in this motif was mutated to a cysteine (C) in Mrs2p, Mg²⁺ transport was strongly reduced.

The figure shows the experimentally determined topology of Mrs2p and Lpe10p as adapted from Bui et al. (
1999) and Gregan et al. (
2001a).
The GMN motif location is indicated in red and the TM domains in light blue.
The orientation in the membrane and the positions of the N- and C-termini are indicated.
The various sizes of the soluble domains are given in amino acids (AA), TM domains are numbered, and the figure is not drawn to scale.

Mrs2p has been localised to the mitochondrial inner membrane by subcellular fractionation and immunodetection and Lpe10p to the mitochondria.
Mitochondria lacking Mrs2p do not show a fast Mg²⁺ uptake, only a slow ‘leak’, and overaccumulation of Mrs2p leads to an increase in the initial rate of uptake.
Additionally, CorA, when fused to the mitochondrial leader sequence of Mrs2p, can partially complement the mitochondrial defect conferred by the loss of either Mrs2p or Lpe10p.
Hence, Mrs2p and/or Lpe10p may be the major Mg²⁺ uptake system for mitochondria.
A possibility is that the proteins form heterodimers, as neither protein (when overexpressed) can fully complement the loss of the other.

The characteristics of Mg²⁺ uptake in isolated mitochondria by Mrs2p were quantified using mag-fura 2.
The uptake of Mg²⁺ by Mrs2p shared a number of attributes with CorA. First, Mg²⁺ uptake was directly dependent on the electric potential (ΔΨ) across the boundary membrane.
Second, the uptake is saturated far below that which the ΔΨ theoretically permits, so the transport of Mg²⁺ by Mrs2p is likely to be regulated in a similar manner to CorA, possibly by the inactivation of the protein.
Third, Mg²⁺ efflux was observed via Mrs2p upon the artificial depolarisation of the mitochondrial membrane by valinomycin.
Finally, the Mg²⁺ fluxes through Mrs2p are inhibited by cobalt (III) hexaammine.

The kinetics of Mg²⁺ uptake by Mrs2p were determined in the Froschauer et al. (
2004) paper on CorA in bacteria.
The initial change in free Mg²⁺ concentration was 150 μM s-1 for wild type and 750 μM s-1 for mitochondria from yeast overexpressing MRS2.
No attempt was made to scale the observed transport to the amount of transporter present.
Like the ALR genes, the MRS2 gene was cloned and sequenced before it was identified as a Mg²⁺ transporter. The MRS2 gene was identified in the nuclear genome of yeast in a screen for suppressors of a mitochondrial gene RNA splicing mutation, and was cloned and sequenced by Wiesenberger et al. (1992). Mrs2p was not identified as a putative Mg²⁺ transporter until Bui et al. (1999). Gregan et al. (2001a) identified LPE10 by homology to MRS2 and showed that both LPE10 and MRS2 mutants altered the Mg²⁺ content of yeast mitochondria and affected RNA splicing activity in the organelle. Mg²⁺ transport has been shown to be directly mediated by Mrs2p, but not for Lpe10p.
The Mrs2p and Lpe10p proteins are 470 and 413 amino acid residues in size, respectively, and a 250–300 amino acid region in the middle of the proteins shows a weak similarity to the full CorA protein. The TM topologies of the Mrs2p and Lpe10p proteins have been assessed using a protease protection assay and are shown in the figure. TM 1 and 2 correspond to TM 2 and 3 in the CorA protein. The conserved GMN motif is at the outside end of the first TM domain, and when the glycine (G) in this motif was mutated to a cysteine (C) in Mrs2p, Mg²⁺ transport was strongly reduced.
The figure shows the experimentally determined topology of Mrs2p and Lpe10p as adapted from Bui et al. (1999) and Gregan et al. (2001a). The GMN motif location is indicated in red and the TM domains in light blue. The orientation in the membrane and the positions of the N- and C-termini are indicated. The various sizes of the soluble domains are given in amino acids (AA), TM domains are numbered, and the figure is not drawn to scale.
Mrs2p has been localised to the mitochondrial inner membrane by subcellular fractionation and immunodetection and Lpe10p to the mitochondria. Mitochondria lacking Mrs2p do not show a fast Mg²⁺ uptake, only a slow ‘leak’, and overaccumulation of Mrs2p leads to an increase in the initial rate of uptake. Additionally, CorA, when fused to the mitochondrial leader sequence of Mrs2p, can partially complement the mitochondrial defect conferred by the loss of either Mrs2p or Lpe10p. Hence, Mrs2p and/or Lpe10p may be the major Mg²⁺ uptake system for mitochondria. A possibility is that the proteins form heterodimers, as neither protein (when overexpressed) can fully complement the loss of the other.
The characteristics of Mg²⁺ uptake in isolated mitochondria by Mrs2p were quantified using mag-fura 2. The uptake of Mg²⁺ by Mrs2p shared a number of attributes with CorA. First, Mg²⁺ uptake was directly dependent on the electric potential (ΔΨ) across the boundary membrane. Second, the uptake is saturated far below that which the ΔΨ theoretically permits, so the transport of Mg²⁺ by Mrs2p is likely to be regulated in a similar manner to CorA, possibly by the inactivation of the protein. Third, Mg²⁺ efflux was observed via Mrs2p upon the artificial depolarisation of the mitochondrial membrane by valinomycin. Finally, the Mg²⁺ fluxes through Mrs2p are inhibited by cobalt (III) hexaammine.
The kinetics of Mg²⁺ uptake by Mrs2p were determined in the Froschauer et al. (2004) paper on CorA in bacteria. The initial change in free Mg²⁺ concentration was 150 μM s-1 for wild type and 750 μM s-1 for mitochondria from yeast overexpressing MRS2. No attempt was made to scale the observed transport to the amount of transporter present.
Magnesium transporter