4 replies to this topic

[alc]

"

 

ABSTRACT

The accumulation of somatic mitochondrial DNA
(mtDNA) mutations contributes to the pathogene-
sis of human disease. Currently, mitochondrial mu-
tations are largely considered results of inaccurate
processing of its heavily damaged genome. However,
mainly from a lack of methods to monitor mtDNA
mutations with sufficient sensitivity and accuracy,
a link between mtDNA damage and mutation has
not been established. To test the hypothesis that
mtDNA-damaging agents induce mtDNA mutations,
we exposed MutaTM Mouse mice to benzo[a]pyrene(B[a]P) or
N-ethyl-N-nitrosourea (ENU), daily for 28
consecutive days, and quantified mtDNA point and
deletion mutations in bone marrow and liver using
our newly developed Digital Random Mutation Cap-
ture (dRMC) and Digital Deletion Detection (3D) as-
says. Surprisingly, our results demonstrate muta-
gen treatment did not increase mitochondrial point
or deletion mutation frequencies, despite evidence
both compounds increase nuclear DNA mutations
and demonstrated B[a]P adduct formation in mtDNA.
These findings contradict models of mtDNA muta-
genesis that assert the elevated rate of mtDNA mu-
tation stems from damage sensitivity and abridged
repair capacity. Rather, our results demonstrate in-
duced mtDNA damage does not readily convert into
mutation. These findings suggest robust mitochon-
drial damage responses repress induced mutations
after mutagen exposure.

 

"

 

... it's time for "question of the month" ... lol

 

 

http://nar.oxfordjou...6.full.pdf html

[corb]

Another win for SENS and Aubrey.
Replication error isn't something we could hope to halt with 21st century science.
So accepting mitochondrial mutations as inevitable and instead figuring out how to limit the damage they cause is the way to go.

Hopefully no more billions of dollars will be wasted in antioxidant and superoxide scavengers research.

It's staggering how often Aubrey is correct about these things.

[alc]

the only "staggering" thing here is that you misunderstands what is happening in the study ... and keep posting

 

you can go and read more in depth and come back when you understand.

[Diocletian]

Is it bad news, can you explain?

[corb]

the only "staggering" thing here is that you misunderstands what is happening in the study ... and keep posting

 

you can go and read more in depth and come back when you understand.

 

The problem is like always - you probably didn't read the paper you posted, and even if you did, I strongly suspect you wouldn't understand it, and in the rare cases you would be able to understand something (I'm yet to witness that happening) you don't have any context to extrapolate from.
 

Let's start with this - the mDNA in the experiment was not mutated but it was damaged beyond a doubt.

 

 

Although the induction of mtDNA damage induced by B[a]P is extensively described, the unexpected lack of mutation induction in mtDNA following B[a]P exposure
prompted us to address the possibility that damage was not induced in our test animals.

...

As adducts formed (hint: that means the mtDNA was damaged) by B[a]P inhibit polymerase extension, we quantified their presence via long-range quantitative PCR

...

A single exposure of 75 mg B[a]P/kg body weight introduced 29 lesions per 10 6 bp in mtDNA with the potential to stall or inhibit polymerase extension

 

 As pointed out in the same paper you posted:

 

 

Thus, as exogenous damage to the mitochondrial genome appears to be a negligible source of induced point and deletion mutations, the majority of mutations induced in mtDNA are likely consequences of endogenous sources of error

 

So if the paper is right on the money - replication error - they seem to have some backing looking at the citations so maybe they are right. Well good. Now mitochondrial mutations move from the esoteric world of the biochemical reactive oxygen species into the arcane world of the mitochondrial genome and all it's endless intricacies.

 

Baring in mind we consider replication error inevitable for nuclear DNA... you know what. Forget it. If you can't draw your own rational conclusions, that's your problem.