The researchers reported in the Journal of Biological Chemistry that they have demonstrated in the laboratory for the first time that in the replication of a subset of genes (the mitochondrial genes) a damaged enzyme makes errors ten-fold to 100-fold more frequently than in healthy individuals.

The researchers compared what happens to a typewriter with a slightly damaged key: "This enzyme frequently makes mistakes while copying the mitochondrial genes, and the accumulation of the mistakes causes the muscle weakness to progress," according to one of the researchers.

This is the first time that such a damaged enzyme -- a DNA synthesis enzyme -- has been shown to play a role in a degenerative disease, in this case a condition called progressive external ophthalmoplegia.

The scientists said that their work applies specifically to this rare affliction in which the eye muscles deteriorate and the patient must move his head, rather than his eyes, to follow an object. However, they said, the principle of repeated, copying errors applies to other mitochondrial degenerative conditions as well, including aging itself.

The answer to the riddle of why degenerative diseases progress with time, the involved muscles getting progressively weaker, has been long in coming:

Nearly 40 years ago, a patient with such a disease was found to have abnormal mitochondria, the main energy-producing component of the cells in the body. Mitochondria play an important role in the proper functioning of energy-hungry organs like the eyes, kidneys and heart and brain.

They act semi-independently from the rest of the cell, and they contain a set of 37 specialized genes on a tiny chromosome. Mutations in any of the mitochondrial genes can caus
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Contact: William (Bill) Grigg
grigg@niehs.nih.gov
301-402-3378
NIH/National Institute of Environmental Health Sciences
6-May-2002