TY - JOUR
T1 - The yeast frataxin homologue mediates mitochondrial iron efflux
T2 - Evidence for a mitochondrial iron cycle
AU - Radisky, Derek C.
AU - Babcock, Michael C.
AU - Kaplan, Jerry
PY - 1999/2/19
Y1 - 1999/2/19
N2 - Mutations in the nuclear gene encoding the mitochondrial protein frataxin are responsible for the neurological disorder Friedreich ataxia (FA). Yeast strains with a deletion in the frataxin homologue YFH1 accumulate excess iron in mitochondria and demonstrate mitochondrial damage. We show that in the absence of YFH1, mitochondrial damage is proportional to the concentration and duration of exposure to extracellular iron, establishing mitochondrial iron accumulation as causal to mitochondrial damage. Reintroduction of YFH1 results in the rapid export of accumulated mitochondrial iron into the cytosol as free, non-heme bound iron, demonstrating that mitochondrial iron in the yeast FA model can be made bioavailable. These results demonstrate a mitochondrial iron cycle in which Yfh1p regulates mitochondrial iron efflux.
AB - Mutations in the nuclear gene encoding the mitochondrial protein frataxin are responsible for the neurological disorder Friedreich ataxia (FA). Yeast strains with a deletion in the frataxin homologue YFH1 accumulate excess iron in mitochondria and demonstrate mitochondrial damage. We show that in the absence of YFH1, mitochondrial damage is proportional to the concentration and duration of exposure to extracellular iron, establishing mitochondrial iron accumulation as causal to mitochondrial damage. Reintroduction of YFH1 results in the rapid export of accumulated mitochondrial iron into the cytosol as free, non-heme bound iron, demonstrating that mitochondrial iron in the yeast FA model can be made bioavailable. These results demonstrate a mitochondrial iron cycle in which Yfh1p regulates mitochondrial iron efflux.
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U2 - 10.1074/jbc.274.8.4497
DO - 10.1074/jbc.274.8.4497
M3 - Article
C2 - 9988680
AN - SCOPUS:0033582421
SN - 0021-9258
VL - 274
SP - 4497
EP - 4499
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -