A DECADE AT AUBURN RESULTS IN BIOCHEMICAL BREAKTHROUGH IN COPPER STORAGE RESEARCH

Dr. Paul Cobine, an associate professor in the Department of Biological Sciences, studies “nutrional science at a cellular level.” His research on the transport of copper within our cells has garnered significant funding from the National Institutes of Health.
by : Jeremy Henderson

Dr. Paul Cobine is so big on analogies, he’ll correlate the popularity of Chick-fil-A to his biochemical experiments on how the body metabolizes copper, the same stuff that’s in batteries and helping to produce the energy you’re using to read this.

“If I sat outside the Student Center and watched students walk out, I would say Chick-fil-A is the only restaurant that we have that serves chicken. That’s like a genetic experiment because I’m just observing what happens,” said Cobine, an associate professor of biological sciences in the College of Sciences and Mathematics. “If I give a student some money and I say ‘can you go in and buy me Chick-fil-A?’ they’ll go in and buy Chick-fil-A and bring it back to me. That’s a biochemical experiment that confirms that Chick-fil-A is there.

“But if I ask a student to just buy me something with chicken, maybe they get it somewhere else. Maybe they buy me a chicken salad from Au Bon Pain, or they go to the Mediterranean Cafe and buy me something with chicken in it. So we just have to make sure we ask the right biochemical questions.”

One of the most fundamental biochemical questions about copper’s role in human health, one that Cobine has been asking since coming to Auburn in 2008, is how the copper your body needs manages to cross the finicky inner membrane of a cell’s mitochondria. Cobine finally found the answer in fall 2017.

“Mitochondria have two membranes, an outer membrane and an inner membrane, and the inner membrane has to be sealed so you can generate energy,” he said. “If you let things cross the inner membrane that basically kills the cell.

“That means that if you want to get across the inner membrane of the mitochondria, you need a transporter.”

Cobine said that by treating the mitochondria of yeast cells, which behave about the same as human cells, he finally identified at least one of those unknown copper transporters—a protein called SLC25A3.

Scientists have known that SLC25A3 smuggles phosphates into the mitochondria, but its newly discovered cargo is an equally important ingredient in the recipe for cytochrome c oxidase, an enzyme that allows your cells to share energy.

Also, without copper, breathing is kind of pointless. “You cannot use oxygen if you don’t have copper,” Cobine said. “So if you lose copper, you remodel the metabolism [of a cell], and that has effects on all sorts of different diseases.”

We’re not just talking general fatigue or wiry hair.

“We expect that understanding this pathway at its base will have impact on heart health, diabetes, Alzheimer’s disease and Parkinson’s disease,” he said, “because all of these diseases are related to mitochondrial function in recruiting copper, and building the copper enzymes that we need in cells is related to having good mitochondrial function.”

Cobine’s findings, which were published in of the Journal of Biological Chemistry, may even have implications for treating some forms of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease.

“We really don’t understand everything that copper does,” he said. “For 10 years, we’ve looked for individual components of copper homeostasis, and we found a transporter that moves copper at one of the critical steps at the end of the copper intake process, but we still don’t understand all of the process.”

Cobine’s continued analysis into the human copper transporter in the mitochondria’s inner membrane is supported by a four-year, $1 million R01 grant from the National Institutes of Health (NIH), a project that aligns perfectly with the agency's continued emphasis on translational “bench-tobedside” medicine.

“We’re really heavily focused on making the discoveries to get to translational steps,” he said. “This first grant set the building blocks to really get towards translational medicine.”

In other words, to start saving lives.

One of Cobine’s long-term goals is to explore the possibility of tweaking SLC25A3 with a targeted drug treatment to render it more or less receptive to copper, depending on a patient’s particular needs.

“There is a chance you can have a trackable target—SLC25A3—and to take a drug to turn this protein on and off,” he said. “And I can change your response to excess or deficiency of copper, absolutely.”

Is the discovery’s translational potential enough to call it a breakthrough?

“It’s a breakthrough because we spent a long time with the transporters and we know how copper gets in [the mitochondria], therefore we start to ask questions about what happens when it doesn’t get in, and that’s a breakthrough,” he added. “It’s an important result that we were super excited about, that reviewers at NIH were excited about.”

Cobine said his research also appealed to the NIH because it is essentially “nutritional science at a cellular level.”

“All the copper we get comes from our diet,” he said. “We take up small amounts every day from lots of different sources.”

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