THE ABC TRANSPORTER ATM1P IS REQUIRED FOR MITOCHONDRIAL IRON HOMEOSTASIS

The function of the,IBC transporter Atm1p located in the mitochondrial inner membrane is not Set known. To study its cellular role, we analy zed a mutant in which ATM1 was disrupted, Delta atm1 cells are deficie nt in the holoforms, but not the apoforms of heme-carrying proteins bo th within and outside mitochondria, yet both synthesis and transport o f heme are functional, Delta atm1 cells are hypersensitive for growth in the presence of oxidative reagents, and they contain increased leve ls of the antioxidant glutathione, in particular of its oxidized form, Mitochondria deficient in Atm1p accumulate 30-fold higher levels of f ree iron as compared to wild-type organelles, i.e. threefold more than mitochondria deficient in frataxin, the protein mutated in Friedreich 's ataxia, The increased mitochondrial iron content may be causative o f the oxidative damage of heme-containing proteins in Delta atm1 cells , Our data assign an important function to Atm1p in mitochondrial iron homeostasis. (C) 1997 Federation of European Biochemical Societies.