cron-web.org

[A1CR]

[2003-06-29; on behalf of CRON4healthyfuture]

Mitochondrial repair is mediated by genes in nucleus; Let's get out of the "common deletion" clouds and come back down to Earth

Look, good ol' fashioned nuclear DNA lesions can generate mitochondrial
dysfunction through aberant DNA repair. So let's keep it real, and not
resort to "mitochondrial sophistry" to explain aging, okay?

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J Biol Chem. 2003 Jun 22 [Epub ahead of print]. Related Articles, Links

Compromised incision of oxidized pyrimidines in liver mitochondria of mice
deficient in NTH1 and OGG1 glycosylases.

Karahalil B, De Souza-Pinto NC, Parsons JL, Elder RH, Bohr VA.

Laboratory of Molecular Gerontology, National Institute on Aging, NIH,
Baltimore, MD 21224.

Mitochondrial DNA is constantly exposed to high levels of endogenously
produced reac-tive oxygen species, resulting in elevated levels of
oxidative damaged DNA bases. A large spectrum of DNA base alterations can
be detected after oxidative stress, and many of these are highly mutagenic.
Thus, an efficient repair of these is necessary for survival. Some of the
DNA repair pathways involved have been characterized, but others are not
yet determined. A DNA repair activity for thymine glycol and other oxidized
pyrimidines has been described in mammalian mitochondria, but the nature of
the glycosylases involved in this pathway remains unclear. The generation
of mouse strains lacking mNTH1 and/or mOGG1, the two major DNA N-
glycosylase/AP-lyases involved in the repair of oxidative base damage in
the nucleus, has provided very useful biological model systems for the
study of the function of these and other glycosylases in mitochondrial DNA
repair. In this study, mouse liver mitochondrial extracts were generated
from mNTH1, mOGG1 - deficient mice, in order to ascertain the role of each
of these glycosy-lases in the repair of oxidized pyrimidine base damage. We
also characterized for the first time the incision of various modified
bases in mitochondrial extracts from the double knockout, [mNTH1, mOGG1]-
deficient, mouse. We demonstrate that mNTH1 is the only glycosylase/AP
lyase responsible for the repair of thymine glycols in mitochondrial DNA,
while other glycosylase/AP lyases also participate in removing other
oxidized pyrimidi-nes, such as 5-hydroxycytosine and 5-hydroxyuracil. We
did not detect a backup glyco-sylase or glycosylase/AP lyase activity for
thymine glycol in the mitochondrial mouse ex-tracts.

PMID: 12819227 [PubMed - as supplied by publisher]