Leary and his team found that mitochondria, the power plants inside all living cells, help regulate the essential element copper, and that those levels must be kept in perfect balance to keep the cell healthy.
"Perturbations in copper handling—be it acquisition, distribution or excretion—cause severe, fatal forms of human disease," said Leary, a biochemist in the College of Medicine. "It is clear that intricate mechanisms exist to safely chaperone copper throughout the body. However, we know shockingly little about these mechanisms."
Mitochondria are emerging as central players in keeping copper levels perfectly balanced, a state called homeostasis, Leary explained. His team's latest work unveils a connection between how mitochondria handle copper and how the cell decides to import more of the element.
Specifically, they looked at the gene Sco1, whose proper functioning is essential to copper homeostasis. They found a novel connection between the gene and a molecule called CTR1, which is responsible for importing copper into the cell. When they disrupted the Sco1 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's critical to central nervous system development, to the end of life, where its proper function is essential to cognition and retaining memory.
"You have about 30 proteins in the cell that require copper as a structural or catalytic factor," Leary said, adding copper dysregulation is at the root of a multitude of illnesses.
Rare genetic flaws involving copper metabolism cause Menkes disease, whose deficient victims rarely live to see their 10th birthday, and Wilson disease, whose surfeit 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 that copper is also part of the immune system's arsenal, used in the oxidative burst that cells unleash to repel 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."
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For more information, contact:
Jennifer Thoma
Media Relations
University of Saskatchewan
306-966-1851
jennifer.thoma@usask.ca
Shedding light on copper's life-and-death balancing act
University of Saskatchewan researcher Scot Leary has begun to shed light on a little-understood process critical to life—how cells regulate copper.