Enzyme could help prevent mitochondria-related diseases. The Dallas Morning News (via Knight-Ridder/Tribune News Service); 2/7/2005 Byline: Sue Goetinck Ambrose DALLAS _ Shut down a power plant, and a city suffers. Shut down the body's power plants, and the body suffers. Scientists have discovered a power plant protector, a finding that could one day help thwart diseases caused by problems with energy production in the body. Trouble in the body's power plants _ tiny structures called mitochondria tucked inside cells _ has been linked to cardiovascular disease, neurological disorders, diabetes and symptoms of aging. Inherited mutations in genes housed inside mitochondria also cause diseases that can affect muscles, vision and other body functions. So scientists are keen on figuring out how cells protect these mitochondrial genes, which are central to energy production. In Friday's issue of the journal Science, researchers from the University of Texas Southwestern Medical Center at Dallas report on an enzyme that appears to coat and protect the genes. Studies like these will be crucial for scientists to treat diseases that are caused by problems with mitochondria, said Gerald Shadel, a molecular biologist at Yale University in New Haven, Conn., familiar with the work "It's grossly underestimated, the effect that dysfunction of mitochondria have on human health," he said. "Understanding that is going to be very, very important." In the new research, a team of scientists led by UT Southwestern molecular biologist Ronald Butow studied mitochondria in yeast, one-celled fungi that are nevertheless quite similar to cells in the human body. Mitochondria in all species contain genes (made of the chemical DNA) that help make key components in the cell's energy production line. Curious as to how cells protect these all-important genes, Dr. Butow and his colleagues examined mitochondrial DNA from yeast to see what was at work. The scientists uncovered more than 20 different proteins coating the DNA. Several of the proteins were already known as enzymes that work in the mitochondria to produce energy. Dr. Butow's team focused on one of them, an enzyme called aconitase. Experiments showed that yeast that were genetically altered so they couldn't produce aconitase didn't pass on mitochondria properly as the cells divided. After a series of divisions, the mitochondria disappeared altogether. Dr. Butow believes that's because aconitase wasn't there to protect the DNA. "What's clear is you've got to keep mitochondrial DNA happy and make sure it's inherited properly as cells divide so they can keep making energy," Dr. Butow said. Understanding how cells protect their mitochondrial DNA so that it can be passed on to newly formed cells could be important in treating diseases caused by mutations in that DNA, Butow said. Each cell in the body can house up to 1,000 mitochondria, each with a copy of mitochondrial DNA. Scientists have found that people who carry mutations in mitochondrial DNA often also have non-mutated copies. The higher the proportion of mutated copies, the worse the symptoms usually are. "This is a problem of how DNA is parceled out," Butow said. If a patient's cells would pass on mostly normal mitochondrial DNA with each new round of cell division, symptoms would be milder. If mutant mitochondrial DNA gets passed on, symptoms are more severe. An understanding of how aconitase, and probably other factors, help mitochondrial DNA get passed on to newly formed cells might give scientists new ideas for treating disease or symptoms of aging. ___ (c) 2005, The Dallas Morning News. Visit The Dallas Morning News on the World Wide Web at http://www.dallasnews.com/ Distributed by Knight Ridder/Tribune Information Services. For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail reprints@krtinfo.com. COPYRIGHT 2005 The Dallas Morning News