Mg2+ Transport, Homeostatasis, Physiology

Magnesium (Mg2+) is the second most abundant cation in cells. Studies on its roles in physiology and medicine were hampered by the fact that genes encoding proteins for Mg2+ transport across membranes were unknown until very recently. We have identified the first known gene for a eukaryotic Mg2+ transport protein, named Mrs2p. It is a member of a large, varied CorA/Mrs2/Alr1 gene family. In yeast and humans Mrs2p constitutes the major channel for Mg2+ influx into mitochondria. Its function is essential for life of mammalian cells. Here we want to further characterize the structure of the Mrs2 channel and mechanisms used by this protein to control mitochondrial Mg2+ homeostasis. This will involve mutation of the Mrs2p channel protein at various sites and the determination of ion fluxes. Mg2+ shortage in cells and organelles results in death of mammalian cells. We aim at understanding which cellular or mitochondrial functions are particularly sensitive to Mg2+ shortage. By use of genome-wide gene expression profiling we will analyse regulatory networks activated in response to Mg2+ deprivation. This work will contribute to a better understanding of magnesium homeostasis and its roles for various functions in human cells.

Magnesium (Mg2+) is the second most abundant cation in cells. Studies on its roles in physiology and medicine were hampered by the fact that genes encoding proteins for Mg2+ transport across membranes were unknown until very recently. We have identified the first known gene for a eukaryotic Mg2+ transport protein, named Mrs2p. It is a member of a large, varied CorA/Mrs2/Alr1 gene family. In yeast and humans Mrs2p constitutes the major channel for Mg2+ influx into mitochondria. Its function is essential for life of mammalian cells. Here we want to further characterize the structure of the Mrs2 channel and mechanisms used by this protein to control mitochondrial Mg2+ homeostasis. This will involve mutation of the Mrs2p channel protein at various sites and the determination of ion fluxes. Mg2+ shortage in cells and organelles results in death of mammalian cells. We aim at understanding which cellular or mitochondrial functions are particularly sensitive to Mg2+ shortage. By use of genome-wide gene expression profiling we will analyse regulatory networks activated in response to Mg2+ deprivation. This work will contribute to a better understanding of magnesium homeostasis and its roles for various functions in human cells.