By Sarah Fecht
The mitochondria inside our cells use the food we eat and the oxygen we breathe to provide energy. It's vital to our survival, and yet sometimes this process goes awry. Every year, about 4,000 children in the United States are born with an inherited mitochondrial disorder—that is, their cells can't provide energy properly. The resulting byproducts may damage organs and cause developmental delays, seizures and even blindness.
Biologist Heather Fiumera of Binghamton University in NY, thinks that some of those health problems may lie in the fact that mitochondrial function requires the cooperation of two different genomes.
Every human inherits two genomes: one in the cell's nucleus, which is a mix of mom's and dad's DNA, and a different one in the mitochondria, which contains a replica of mom's mitochondrial DNA.
"It may be that some combinations of mitochondrial and nuclear genomes work together more efficiently than others," Fiumera says. "While mutations in either genome may affect mitochondrial function, they don't explain the whole story. You might inherit a mitochondrial genome that helps you become a world-class marathon runner, but your brother"—who would have the exact same mitochondrial genome as you—"might not be as successful, even with the same training."
Similarly, a mitochondrial mutation may cause a severe metabolic disorder in one sibling but mild symptoms in another because of how the mitochondrial mutation interacts with their different nuclear DNAs.
The reason that mitochondrial DNA and nuclear DNA have such unpredictable interactions might be because the genomes originated from two different organisms. Scientists believe that a mitochondrion has its own DNA because it was once a free-living bacterium that was engulfed by another cell.
But instead of becoming dinner, the mitochondrion was co-opted to provide energy for its predator. The two cells managed to work together and, over time, became dependent upon one another.
Mitochondria have inserted some of their genes into the nucleus, and the nucleus uses protein messengers to control how much energy the mitochondrion produces and how it does its job. It may be that the two genomes are still co-evolving and learning the best ways to live together peacefully.
Fiumera studies these interactions in yeast, a single-celled fungus that is commonly used as a model organism in biomedical research. Using powerful genetic tools developed for studying genetics in yeast, Fiumera is able to mix and match mitochondrial and nuclear genomes. Her goal is to discover whether certain combinations of the two genomes produce yeast that is especially hardy, able to thrive even when starved, heated or poisoned.
So far, Fiumera has examined only a handful of different combinations and has already found that mitochondrial nuclear interactions are responsible for as much as 20 percent of the differences in growth rates between yeast cells. She now plans to buy laboratory equipment that will allow her to scale up the research, measuring growth rates in about 200 samples at once. She predicts that her team will collect more than 10,000 growth rates in just the initial phase of the project.
Fiumera then plans to map the genes involved in determining how effective each combination is. Eventually, she'd like to see whether yeast cell populations in the wild skew toward certain beneficial mitochondrial-nuclear combinations in the same way that plants and animals genetically adapt to their environments.
But Fiumera won't be doing all of this work alone.
"This project is a marriage between yeast genetics and population biology, and it is enhanced by my actual marriage to a population geneticist," she jokes, referring to her husband, Binghamton biologist Anthony Fiumera, who is collaborating on the project. Binghamton computer scientist Kenneth Chiu is lending his expertise to help the biologists parse through huge data sets.
Since energy is so vital to a cell's functioning, mitochondrial genes and machinery tend to be highly similar in organisms as far-flung as yeast and humans. That allows Fiumera to hope that one day her research will be used to devise treatments for people who are suffering from debilitating metabolic disorders.
"You have to understand the mechanism behind a problem," she says, "before you can fix the problem."
Adapted with permission from Binghamton University Magazine .