Magnesium transporter MRS2 homolog, mitochondrial (MRS2)

Magnesium transporter MRS2 homolog, mitochondrial (MRS2) is a pentameric, nonselective ion channel of the CorA family embedded in the inner mitochondrial membrane in mammalian cells. Unlike its prokaryotic correlates, it is regulated primarily by Ca²⁺ and exhibits permeability to Mg²⁺, Ca²⁺, Na⁺, and K⁺ ions. MRS2 plays a central role in mitochondrial magnesium homeostasis, which is essential for various mitochondrial functions including stabilization of mitochondrial DNA, RNA splicing, and ATP synthesis. Loss of MRS2 results in marked mitochondrial morphological changes, disrupted bioenergetics, and disease phenotypes associated with mitochondrial dysfunction. Its unique channel structure includes a conserved arginine ring that regulates cation movement and prevents collapse of the proton motive force vital for ATP production. Experimental inhibition of this channel is possible, but currently, no approved drugs target MRS2 directly and safety considerations are theoretical, mostly related to disruption of mitochondrial function.

Other names

MRS2HPTMRS2LMRS2-like proteinMagnesium homeostasis factorPutative magnesium transporter

Inhibition of Mg²⁺ transport via channel blockade (e.g., cobalt hexammine); Modulation of cation conductance through channel regulation (possible Cl⁻-mediated mechanism).