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Mech Ageing Dev. 2004 Jun;125(6):417-20. Related Articles, Links
Mitochondrial oxidative stress can lead to nuclear hypermutability.
Hartman P, Ponder R, Lo HH, Ishii N.
Biology Department, Texas Christian University, Fort Worth, TX 76129, USA.
Reactive oxygen species (ROS) are generated in mitochondria and are thought to
be important in aging, carcinogenesis, and the development of other
pathologies. We now provide direct experimental evidence linking mitochondrial
ROS generation to the induction of nuclear DNA damage and subsequent
mutagenesis of a chromosomal gene. Specifically, we demonstrate that the mev-1
mutant of Caenorhabditis elegans has elevated levels of oxidative damage in its
chromosomal DNA. This mutant was shown previously to overproduce ROS in its
mitochondria. We also show that mutation frequencies were higher in the mev-1
mutant under hypoxia than in the wild type strain. By extension, these data
imply that mitochondrially derived ROS mutate other genes, including tumor
suppressor genes and oncogenes. We propose that this three-step process
(mitochondrial ROS --> nuclear DNA damage --> mutation) contributes to aging
and age-associated diseases.
PMID: 15178131 [PubMed - in process]
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Tom
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Mitochondrial oxidative stress can lead to nuclear hypermutability.
Hartman P, Ponder R, Lo HH, Ishii N.
Biology Department, Texas Christian University, Fort Worth, TX 76129, USA.
Reactive oxygen species (ROS) are generated in mitochondria and are thought to
be important in aging, carcinogenesis, and the development of other
pathologies. We now provide direct experimental evidence linking mitochondrial
ROS generation to the induction of nuclear DNA damage and subsequent
mutagenesis of a chromosomal gene. Specifically, we demonstrate that the mev-1
mutant of Caenorhabditis elegans has elevated levels of oxidative damage in its
chromosomal DNA. This mutant was shown previously to overproduce ROS in its
mitochondria. We also show that mutation frequencies were higher in the mev-1
mutant under hypoxia than in the wild type strain. By extension, these data
imply that mitochondrially derived ROS mutate other genes, including tumor
suppressor genes and oncogenes. We propose that this three-step process
(mitochondrial ROS --> nuclear DNA damage --> mutation) contributes to aging
and age-associated diseases.
PMID: 15178131 [PubMed - in process]
--------------------------------------------------------------------------
------
Who loves ya.
Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking