PMID- 10589829
OWN - NLM
STAT- MEDLINE
DCOM- 19991228
LR  - 20190725
IS  - 0026-8925 (Print)
IS  - 0026-8925 (Linking)
VI  - 262
IP  - 3
DP  - 1999 Oct
TI  - A mutation in a mitochondrial ABC transporter results in mitochondrial
      dysfunction through oxidative damage of mitochondrial DNA.
PG  - 426-36
AB  - We have isolated a Saccharomyces cerevisiae mutant that shows an increased
      tendency to form cytoplasmic petites (respiration-deficient rho- or rho0 mutants)
      in response to treatment of cells growing on a solid medium with the DNA-damaging
      agent methyl methane-sulfonate or ultraviolet light. The mutation in this strain,
      atm1-1, was found to cause a single amino acid substitution in ATM1, a nuclear
      gene that encodes the mitochondrial ATP-binding cassette (ABC) transporter. When 
      the mutant cells were grown in liquid glucose medium, they accumulated free iron 
      within the mitochondria and at the same time gave rise to spontaneous cytoplasmic
      petite mutants, as seen previously in cells carrying a mutation in a gene
      homologous to the human gene responsible for Friedreich's ataxia. Analysis of the
      effects of free iron and malonic acid (an inhibitor of oxidative respiration in
      mitochondria) on the incidence of petites among the mutant cells indicated that
      spontaneous induction of petites was a consequence of oxidative stress rather
      than a direct effect of either a defect in the ATM1 gene or the accumulation of
      free iron. We observed an increase in the incidence of strand breaks in the
      mitochondrial DNA of the atm1-1 mutant cells. Furthermore, we found that rates of
      induction of petites and accumulation of strand breaks in mitochondrial DNA were 
      enhanced in the atm1-1 mutant by the introduction of another mutation, mhr1-1,
      which results in a deficiency in mitochondrial DNA repair. These observations
      indicate that spontaneous induction of petites in the atm1-1 mutant is a
      consequence of oxidative damage to mitochondrial DNA mediated by enhanced
      accumulation of mitochondrial iron.
FAU - Senbongi, H
AU  - Senbongi H
AD  - Cellular and Molecular Biology Laboratory, Riken Institute, Saitama, Japan.
FAU - Ling, F
AU  - Ling F
FAU - Shibata, T
AU  - Shibata T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Mol Gen Genet
JT  - Molecular & general genetics : MGG
JID - 0125036
RN  - 0 (ATM1 protein, S cerevisiae)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Fungal Proteins)
RN  - 0 (Mutagens)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - AT5C31J09G (Methyl Methanesulfonate)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - ATP-Binding Cassette Transporters/genetics/*metabolism
MH  - Amino Acid Sequence
MH  - Cloning, Molecular
MH  - Crosses, Genetic
MH  - *DNA Damage
MH  - *DNA Repair
MH  - DNA, Mitochondrial/*metabolism
MH  - Fungal Proteins/genetics/*metabolism
MH  - Genetic Complementation Test
MH  - Iron/metabolism
MH  - Methyl Methanesulfonate/pharmacology
MH  - Mitochondria/*genetics
MH  - Molecular Sequence Data
MH  - Mutagens/pharmacology
MH  - Mutation
MH  - Oxidative Stress
MH  - Oxygen Consumption/genetics
MH  - Saccharomyces cerevisiae/drug effects/*genetics/radiation effects
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
MH  - Ultraviolet Rays
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1007/s004380051102 [doi]
PST - ppublish
SO  - Mol Gen Genet. 1999 Oct;262(3):426-36. doi: 10.1007/s004380051102.