Aconitase Plays Two Roles in Cellular Metabolism

Researchers have found that aconitase, the enzyme in the Kreb's cycle that converts citrate to isocitrate, plays an important role in maintaining the integrity of the DNA that makes up the mitochondrial genome.

The mitochondrial genome in humans comprises 37 genes. Twenty-four of the genes specify RNA molecules involved in protein synthesis while the remaining 13 encode proteins required for the biochemical reactions that make up respiration. A number of rare diseases are caused by mutations in mitochondrial DNA, and the tissues primarily affected are those that most rely on respiration, i.e., the brain and nervous system, muscles, and the kidneys and liver. All mitochondrial diseases are maternally inherited, since all the mitochondria in the developing human embryo come from the egg. There are no mitochondria in the sperm head, which carries the paternal half of the nuclear genome.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) worked with a yeast model to study the behavior of aconitase. They found that the enzyme's catalytic activity was separate from its function in DNA maintenance. As aconitase is manufactured in the cytoplasm and then transported into the mitochondria, the investigators speculated that it might be part of the cell's retrograde signaling network. These findings were published in the February 4, 2005, edition of Science.

"Mitochondrial DNA was discovered in the 1960s, and we still do not know much about how it is organized, packaged, or inherited,” said senior author Dr. Ronald Butow, professor of molecular biology at the University of Texas Southwestern Medical Center. "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.”




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University of Texas Southwestern Medical Center