Researchers at UT Southwestern discover new function for old enzyme

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Medical News Today 04 Feb 2005

Researchers at UT Southwestern discover new function for old enzyme

In a step toward understanding the early evolution of the cell, researchers at

UT Southwestern Medical Center have discovered that an enzyme important in the

production of energy also protects the mitochondria, the energy factory itself.

The enzyme, called aconitase, is a well-known component of the pathway in cells

that produces energy. But in a study using baker's yeast, Dr. Butow,

professor of molecular biology, has shown a new function for the enzyme -

keeping the mitochondrial genome intact.

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

Mitochondria are the powerhouses of cells and create energy for all cellular

processes. It is thought that mitochondria are descended from bacteria that

originally took up residence in early cells. Through elements of a

little-understood symbiotic relationship between the bacteria and the cell, the

bacteria lost their independence and evolved into an organelle that provides

energy for the cell. The relationship between mitochondria and the cell make

each vital to the other's survival, and may explain a key biological event - the

development of an efficient energy producer to fuel the evolution of more

complex life forms.

Because of their supposed microbial origins, mitochondria have their own DNA,

which is separate from the DNA in the cell nucleus. Cells that have lost their

mitochondrial DNA do not pass on working mitochondria when they divide. Without

working mitochondria, cells cannot produce energy efficiently. Events that lead

to mitochondrial DNA defects are associated with neuromuscular diseases and

premature aging disorders in humans.

" Mitochondrial DNA was discovered in the 1960s, and we still do not know much

about how it is organized, packaged or inherited, " said Dr. Butow. " What is

really amazing is that we very recently discovered proteins associated with

mitochondrial DNA that were thought to only have metabolic functions, and that

aconitase, one of these proteins, is essential for mitochondrial DNA maintenance

and inheritance, a new function independent of its normal enzyme activity. "

To determine the region of aconitase that keeps mitochondrial DNA intact, Dr.

Butow's group made mutations in parts of the enzyme that are important for its

catalytic activity. In spite of these mutations, aconitase still functions in

the maintenance of mitochondrial DNA. The researchers concluded that aconitase's

role in protecting the mitochondrial genome is independent of its role in making

energy, giving a new face to the long-known enzyme.

Genes in the cell's nucleus code for aconitase, and once made, the protein is

shuttled to the mitochondria to serve its functions. According to Dr. Butow,

aconitase may participate in an internal cell communication system known as

retrograde signaling.

Retrograde signaling serves as a status-check in cells, where the mitochondria

signal to the nucleus if something is wrong and when things are better again. By

protecting the mitochondrial DNA, aconitase may be part of the " A-OK " signal

after the cell experiences stress.

The role of aconitase in stabilizing the mitochondrial genome may be an

evolutionary adaptation where the mitochondria co-opts a nuclearly encoded

protein to ensure survival of its genome, said Dr. Butow. " The cell takes care

of the nucleus, because that is where its genome is, " he said, " but the

mitochondrial genome is not looked after. It has to take care of itself. "

Other UT Southwestern researchers who participated in the study are lead author

Dr. Xin Jie Chen, assistant professor of molecular biology, and Xiaowen Wang,

research assistant in molecular biology. Dr. Brett A. Kaufmann, a former

graduate student at UT Southwestern now with the Montreal Neurological

Institute, also contributed.

The study was supported by the National Institutes of Health.