Scot Leary

Copper's quirks

University of Saskatchewan researcher Scot Leary has begun to shed light on a little-understood process critical to life—how cells regulate copper.

By Michael Robin
"You have about 30 proteins in the cell that require copper," said Leary, a biochemist in the College of Medicine, adding that copper dysregulation is at the root of a multitude of illnesses, including Lou Gehrig's disease and dementia. The body's cells also use copper to fight off infections.

Changes in the way the body handles copper, "be it acquisition, distribution or excretion, cause severe, fatal forms of human disease," Leary said, explaining that there are intricate mechanisms to move copper around the body. "However, we know shockingly little about these mechanisms."

Leary and his team demystified copper somewhat with their discovery that mitochondria, the power plants inside all living cells, help to balance levels of the essential element to keep the cell healthy.

Specifically, they looked at the gene Sco1, and found a novel connection between it and a molecule responsible for importing copper into the cell. When they disrupted the gene in a mouse model, it caused a severe copper deficiency, and cells could not make the proteins they needed to make energy—a lethal condition. Their work is published in the journal Cell Reports.

According to Leary, copper is a Swiss Army knife of elements when it comes to the body's chemistry, beginning in the womb where it is critical to central nervous system development, to the end of life where its proper function is essential to cognition and retaining memory.

Rare genetic flaws involving copper metabolism cause Menkes disease, whose victims rarely live to see their 10th birthday, and Wilson disease, where an excess of copper can be treated. More common is amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, caused by dysfunction in an essential copper-related protein. Leary explained copper is also part of the immune system's arsenal used to attack invading bacteria, viruses or fungi.

"Copper is turning out to be really big at the host-pathogen interface, " he said. "Pathogens are more virulent if they're able to kick copper out that the host throws at them. We don't really understand the interplay between host and pathogen in this context and how that may be manipulated in our favour."

Leary said there is also a growing body of evidence that dysfunctional copper regulation is involved in some types of dementia in older adults.

"Copper is turning out to be important to brain physiology and there is clear and exciting evidence that late-onset, cognitive disorders with neurodegeneration involve dysregulation of copper homeostasis."