Health: When Cells Stop Working

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Exactly what role mitochondria play in these illnesses is still unclear. It's not even certain whether mitochondrial breakdowns are the cause or the effect of disease--although researchers suspect it's often a little of both. As mitochondria process food into energy, they create free radicals--highly reactive oxygen ions that can cause damage to proteins. Many experts believe that as cells age, this damage accumulates, weakening the mitochondria irrevocably and doing harm to specific organs--or, more generally, to the whole body. There's no smoking gun yet, says Mootha, but there's some tantalizing evidence. "We do know," he says, "that exercise can help slow the damage from diabetes and other disorders and also that exercise boosts the function of mitochondria."

In the known mitochondrial diseases, though, it's clearly a genetic abnormality that almost always sets things off. Mitochondria are different from the rest of the cell in that they have their own DNA, inherited directly from the mother (with no input from the father) that's entirely separate from the DNA in the nucleus. Evolutionary biologists suspect, in fact, that these organelles started out as independent bacteria that were absorbed long ago into cells and harnessed as energy factories.

By the mid-1980s, says Mootha, the mitochondrial genome--with only about 16,000 genetic "letters," compared with 3 billion in the nuclear genome--had been sequenced. That let researchers link specific, rare disorders to specific mitochondrial mutations, always passed from mother to child. But by the time the Human Genome Project was completed in 2000, it was clear that mutations in the nucleus could cause problems in the mitochondria as well. "We now estimate," says Mootha, "that while mitochondrial DNA encodes just 13 proteins, another 1,500 or so proteins used by mitochondria are encoded by the nucleus."

This helps explains why mitochondrial disease occurs in such bewildering variety and why it can be so difficult to diagnose. Even now that it's better understood, parents sometimes face doctors' accusations of deliberately poisoning children to draw attention to themselves.

There's no cure yet for mitochondrial disease, nor even a surefire treatment. Sufferers are usually given vitamin and nutritional supplements, which can help slow the progress of the illness, but they aren't always effective. "If you'd asked me a year ago," says Shoffner, "I would have said that's the only option." Since then, however, some promising drugs have been developed, and will soon go into clinical trials. And a new company called Edison Pharmaceuticals, of San Jose, Calif., was founded last year for the sole purpose of coming up with drugs for mitochondrial disease.