Researchers at = UT Southwestern discover new function for old enzyme

Researchers=20 at UT Southwestern discover new function for old=20 enzyme

DALLAS - = Feb. 3,=20 2005 - In a step toward understanding the early evolution of the = cell,=20 researchers at UT Southwestern Medical Center have discovered that = an=20 enzyme important in the production of energy also protects the=20 mitochondria, the energy factory itself.

The enzyme, called = aconitase, is a well-known component of the = pathway in=20 cells that produces energy. But in a study using baker's = yeast, Dr. Ronald Butow, professor of molecular = biology, has=20 shown a new function for the enzyme - keeping the mitochondrial = genome=20 intact.

The study is available online and in the Feb. 4 = edition of=20 the journal Science.

Xiaowen Wang=20 (left), Dr. Ron Butow, professor = of=20 molecular biology (middle), and Dr. Xin=20 Jie Chen (right), assistant = professor of=20 molecular biology, report that mitochondria, the cell's = power plant,=20 utilizes a protein called aconitase to=20 maintain its DNA. Protecting mitochondrial DNA is important = in=20 ensuring that it works properly, and may prevent aging and=20 neurological diseases.=20

Mitochondria=20 are the powerhouses of cells and create energy for all cellular = processes.=20 It is thought that mitochondria are descended from bacteria that=20 originally took up residence in early cells. Through elements of a = little-understood symbiotic relationship between the bacteria and = the=20 cell, the bacteria lost their independence and evolved into an = organelle=20 that provides energy for the cell. The relationship between = mitochondria=20 and the cell make each vital to the other's survival, and may = explain a=20 key biological event - the development of an efficient energy = producer to=20 fuel the evolution of more complex life = forms.

Because of=20 their supposed microbial origins, mitochondria have their own DNA, = which=20 is separate from the DNA in the cell nucleus. Cells that have = lost=20 their mitochondrial DNA do not pass on working mitochondria when = they=20 divide. Without working mitochondria, cells cannot produce energy=20 efficiently. Events that lead to mitochondrial DNA defects are = associated=20 with neuromuscular diseases and premature aging disorders in=20 humans.

"Mitochondrial DNA was discovered in the 1960s, and = we=20 still do not know much about how it is organized, packaged or = inherited,"=20 said Dr. Butow. "What is really = amazing is that=20 we very recently discovered proteins associated with mitochondrial = DNA=20 that were thought to only have metabolic functions, and that aconitase, one of these proteins, is = essential for=20 mitochondrial DNA maintenance and inheritance, a new function = independent=20 of its normal enzyme activity."

To determine the region of = aconitase that keeps mitochondrial DNA = intact, Dr.=20 Butow's group made mutations in parts = of the=20 enzyme that are important for its catalytic activity. In spite of = these=20 mutations, aconitase still functions = in the=20 maintenance of mitochondrial DNA. The researchers concluded that = aconitase's role in protecting the = mitochondrial=20 genome is independent of its role in making energy, giving a new = face to=20 the long-known enzyme.

Genes in the cell's nucleus code for = aconitase, and once made, the protein is = shuttled to=20 the mitochondria to serve its functions. According to Dr. Butow, aconitase = may=20 participate in an internal cell communication system known as = retrograde=20 signaling. Retrograde signaling serves as a status-check in cells, = where=20 the mitochondria signal to the nucleus if something is wrong and = when=20 things are better again. By protecting the mitochondrial = DNA, aconitase may be part of the "A-OK" signal = after the=20 cell experiences stress.

The role of aconitase in stabilizing the mitochondrial = genome may=20 be an evolutionary adaptation where the mitochondria co-opts a = nuclearly encoded protein to ensure survival = of its=20 genome, said Dr. Butow. "The cell = takes care of=20 the nucleus, because that is where its genome is," he said, "but = the=20 mitochondrial genome is not looked after. It has to take = care of=20 itself."

Other UT Southwestern researchers who participated = in the=20 study are lead author Dr. Xin Jie Chen, assistant professor of molecular = biology,=20 and Xiaowen Wang, research assistant = in=20 molecular biology. Dr. Brett A. Kaufmann, a former graduate = student at UT=20 Southwestern now with the Montreal Neurological Institute, also=20 contributed.

The study was supported by the National = Institutes of=20 Health.

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Media=20 Contact: Megha Satyanarayana
214-648-3404
e-mail: megha.saty@utsouthwestern.edu