Researchers have solved the 100-year-old mystery of what activates magnesium ions in the cell. The discovery is expected to be a springboard for future development of novel drugs to treat cardiovascular disease, metabolic disorders such as diabetes, and other diseases.

Reporting in Cell, scientists said the magnesium activator is a metabolite called lactate, which is elevated in the blood during intense exercise and in many diseases, including heart disease, diabetes, sepsis and cancer.

"Lactate is a signal that - like a light switch - turns on magnesium ions," said lead author. "On lactate's signal, the ions rush out of cellular storehouses called the endoplasmic reticulum."

The team made a second discovery: A protein called Mrs2 transports the released magnesium ions into cell powerhouses known as mitochondria. These power plants generate ATP, which is the energy currency fueling all the processes in the body.

"We believe this loop is essential for health," said study coauthor. "If there is a problem with magnesium routing, impairments ensue, such as the diminished mitochondrial function and poor energy production observed in Type 2 diabetes or severe infections."

IP3, the activator for calcium ions, was discovered in 1984. Since that time, the calcium field has grown in monumental fashion, whereas magnesium continued to be a riddle, said coauthor.

Summing up the discovery, the senior author said: "Magnesium is essential for life. It's in our blood. It's been implicated in and used as a treatment for a variety of diseases, including migraines, cardiovascular diseases, diabetes and preeclampsia. But to take the next step forward, we needed to understand the dynamics of magnesium in our bodies. With this finding, we believe we have laid out one of the pillars of support that the scientific world needed."

https://www.cell.com/cell/fulltext/S0092-8674(20)31091-6