cytochrome c oxidase and senescence
oberon at vcn.bc.ca
Fri Mar 10 21:12:55 EST 2000
Begel O. Boulay J. Albert B. Dufour E. Sainsard-Chanet A.
Centre de Genetique Moleculaire-Centre National de la Recherche Scientifique,
91198 Gif-sur-Yvette Cedex, France.
Mitochondrial group II introns, cytochrome c
oxidase, and senescence in Podospora anserina.
Molecular & Cellular Biology. 19(6):4093-100, 1999 Jun.
Podospora anserina is a filamentous fungus with a limited life span. It
expresses a degenerative syndrome called senescence, which is always
associated with the accumulation of circular molecules (senDNAs) containing
specific regions of the mitochondrial chromosome. A mobile group II intron
(alpha) has been thought to play a prominent role in this syndrome. Intron
alpha is the first intron of the cytochrome c
oxidase subunit I gene (COX1). Mitochondrial mutants that
escape the senescence process are missing this intron, as well as the first
exon of the COX1 gene. We describe here the first mutant of P. anserina that
has the alpha sequence precisely deleted and whose
cytochrome c oxidase activity is identical
to that of wild-type cells. The integration site of the intron is slightly
modified, and this change prevents efficient homing of intron alpha. We show
here that this mutant displays a senescence syndrome similar to that of the
wild type and that its life span is increased about twofold. The introduction
of a related group II intron into the mitochondrial genome of the mutant does
not restore the wild-type life span. These data clearly demonstrate that
intron alpha is not the specific senescence factor but rather an accelerator
or amplifier of the senescence process. They emphasize the role that intron
alpha plays in the instability of the mitochondrial chromosome and the link
between this instability and longevity. Our results strongly
support the idea that in Podospora, "immortality" can be acquired not by the
absence of intron alpha but rather by the lack of active
cytochrome c oxidase.
Sohal RS. Sohal BH. Orr WC.
Department of Biological Sciences, Southern Methodist University, Dallas, TX
Mitochondrial superoxide and hydrogen peroxide generation, protein oxidative
damage, and longevity in different species of flies.
Free Radical Biology & Medicine. 19(4):499-504, 1995 Oct.
The objective of this study was to further elucidate the role of oxidative
stress in the aging process by determining whether or not the rates of
mitochondrial superoxide anion radical and hydrogen peroxide (H2O2)
production, the activity of cytochrome c
oxidase, and the concentration of protein carbonyls are
correlated with the life span potential of different species. A comparison
was made among five different species of dipteran flies, namely, Drosophila
melanogaster (fruit fly), Musca domestica (house fly), Sarcophaga bullata
(flesh fly), Calliphora vicina (blow fly) and Phaenecia sericata (a species
of blow flies), which range more than 2-fold in their life span potentials.
The average life span potential of these species was found to be inversely
correlated with the rates of mitochondrial superoxide and H2O2 production and
with the level of protein carbonyls, and to be directly related to the
activity of cytochrome c oxidase. The
significance of these findings in context of the validity of the oxidative
stress hypothesis of aging is discussed. It is inferred that longer life span
potential in these insect species is associated with relatively low levels of
oxidant generation and oxidative molecular damage. These results accord with
our previous findings on different mammalian species.
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