Mitochondrial intervention

Magnus Lynch mdl24 at cam.ac.uk
Sun Feb 27 15:14:36 EST 2000


"Paul S. Brookes." wrote:
 
> WRT to adding telemeres into mtDNA, I agree with Aubrey in that there
> are plenty of better ways to stop oxidative damage, such as common
> antioxidants (SOD, GPx, Lipids, GSH) and also physical barriers such
> as membranes, and stopping the ROS at its source.   

I don't think that antioxidants would be very effective as some
superoxide production occurs on the outer surface of the inner
mitochondrial membrane in the mitochondrial intermembrane space (MIMS).
There is no SOD present in the MIMS so it cannot be upregulated. As the
mtDNA is thought to be attached to the inner surface of the inner
mitochondrial membrane ROS could diffuse through the inner mitochondrial
membrane and damage mtDNA before antioxidants could detoxify them. I do,
however think you are right that the mitochondrial membranes would
provide a much more effective sink for ROS than my proposal.

Telomeres would
> seem to be a complicated way to go about things - and something that
> if it worked, you'd think nature would be doing it already.  Maybe
> there's a damn good reason not to have telomeres in mtDNA.

I am sure that both you are Aubrey are correct in saying that this idea
will not work, however I do not think that you can infer that it does
not work simply because evolution has not done it already: It is
believed that a population evolves a rate of aging which is determined
by their mortality from other causes aside from aging. When humans
evolved their longer lifespans, it may have been easier for evolution to
change other determinants of metabolic toxicity such as respiratory
leakiness. This is supported by the observation that there seems to
selective pressure to ensure that there is very little 'junk' DNA in the
mitochondrial genome. Preferentially oxidised sequences would presumably
only provide an extension in lifespan when they constituted a
significant proportion of the mitochondrial genome and they would
probably have been eliminated by the selection against junk DNA before
this stage was reached.

Magnus





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