DELETION OF THE YEAST HOMOLOG OF THE HUMAN GENE ASSOCIATED WITH FRIEDREICHS ATAXIA ELICITS IRON ACCUMULATION IN MITOCHONDRIA

Deletion of YDL120, the yeast homologue of the human gene responsible for Friedreich's ataxia, elicits decreased cellular respiration associ ated with decreased cytochrome c oxidase activity and, in certain nucl ear backgrounds, mitochondrial DNA is lost, In the null mutants, the c ellular growth is highly sensitive to oxidants, such as H2O2, iron and copper, However, only ferrous sulfate elicits loss of mitochondrial D NA, Mitochondria of the null mutants contain 10 times more iron than w ild-type, The neurodegeneration observed in Friedreich's ataxia can be well explained on the basis of a mitochondrial iron overload responsi ble for an increased production of highly toxic free radicals. (C) 199 7 Federation of European Biochemical Societies.