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U. lab studying cells’ energy

Genetic research may help scientists understand diseases

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A University of Utah laboratory has identified genes that help control the production of energy in the living cells that make up everything from yeast to humans.

"There actually are a lot of direct applications for this work," said the lab's chief, Janet M. Shaw, associate professor of biology. "And certainly, if we can map some of the human genes to a disease, then what we learn . . . is going to be very important to understanding what goes wrong in a human cell."

During a recent a "Science at Breakfast" session sponsored by the university science department, Shaw outlined her laboratory's work on mitochondria, structures in a cell that supply energy packets used by the cell in moving or growing. The lab's team, which is funded by the American Cancer Society and the National Institutes of Health, includes two undergraduate students.

Mitochondria "form long, tunnel-like tubes or snake-like structures that continually divide by a process called fission, (and) fuse again," she said. This growth and change is crucial to the cell's delivering energy.

Using genetic methods, the laboratory found genes that control the shape of mitochondria, which is vital to the energy production.

The genes cause production of protein molecules called "Dnm1" and "Fzo1," which are responsible for the action of the tubes. The first triggers fission, or breaking, of the tubes; the second regulates fusion, or the tubes' growing back together.

Mitochondria are "responsible for producing most of the energy that our cells use to grow and function, and for this reason it's often called the powerhouse of the cell," she said.

These structures extract energy from food and store it in a molecule called ATC. When the mitochondria send the molecules into the main section of a cell, the energy "can then be used to build new molecules or larger structures."

Mitochondria often cluster near organs that need a lot of energy. They may supply nerve neurons with the energy they need to function. They wrap around muscle fibers, "and then they provide the energy that you need to contract your muscles," she said.

When the "powerhouse" doesn't function properly, disease results.

In humans, defects in mitochondria can impair brain function, interfere with vision, cause muscle weakness and muscle spasms, or weaken the heart. The defects can cause heart failure, interfere with eating and digestion, and result in death, she added.

"So we're interested in understanding how it is that cells control the mitochondrial shape," she said. The team experiments with cells of budding yeast, the same type used to make bread dough rise.

"Based on those experiments we've done, we've developed a model to explain how these two proteins control the shape of mitochondria in a yeast cell."

The two proteins work together, and if either doesn't perform, problems develop.

If the scientists cause a genetic mutation that blocks the Dnm1 protein (the molecule that causes fission), the breaking does not happen, and "the mitochondria form these elaborate net-like structures."

If a mutation blocks the protein that causes fusion, the mitochondrial tubes just fragment into smaller pieces.

"As it turns out, Dnm1 and Fzo1 are not only found in yeast, and fission and fusion don't only occur in yeast mitochondria," she said.

"If you watch what happens to mitochondria in cells all the way from yeast to humans, you see these types of mitochondrial behavior. And the molecules . . . also trigger fission and fusion in all cell types, including humans."

What scientists learn about microscopic proteins in yeast, she said, someday could help explain why humans develop "a whole variety of mitochondrial diseases that affect neurons and muscles."

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