Error catastrophe in mutant mitochondria

The error catastrophe theory of aging, proposed by Orgel in 1963, predicted a decrease in the fidelity of information transfer that accelerated as aging progressed, until properly functioning macromolecules could no longer be reliably made. The theory was extensively tested by comparing DNA polymerases, transfer RNAs, and proteins derived from aging versus young animals, but it did not prove to have general applicability to the process of aging. Recently, the heritable eye disorder progressive external ophthalmoplegia has been found to result from mutation of the gene encoding DNA polymerase gamma, which replicates mitochondrial DNA. The mutant form of the polymerase replicates DNA less accurately than the wild-type enzyme, providing an explanation for the accumulation of mutations in the mitochondrial DNA of patients with this disorder. The affected mitochondria appear to exhibit an age-dependent error catastrophe. It is possible that other genetic diseases might result in error catastrophes in mitochondria as well.