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Idea out of thin air..


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#1 olaf.larsson

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Posted 22 July 2005 - 01:08 PM


Today when I was sleeping I thought of following..:

The cause that mito genes have not moved in to the nucleus is that if the mito genes get harmed the mito could be killed by mitoptosis. If the genes would be in the nucleus and get mutated it could lead to excessive ROS production in ALL the mitos of the cell. With mito genes in the mito there is a possibility to kill mutated mitos and thus prevent ROS-production. Yes, mitoptosis is a new concept that may not heard about, a search on Altavista gives 50 hits..

Nice idea..dont you think..now lets see if it has any connection to reality..

#2 Mark Hamalainen

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Posted 22 July 2005 - 05:07 PM

Good thinking, here's the earliest reference to mitoptosis on pubmed:

1: Mol Aspects Med. 1999 Jun;20(3):139-84.

Mitochondrial physiology and pathology; concepts of programmed death of
organelles, cells and organisms.

Skulachev VP.

Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical
Biology, Moscow State University, Russian Federation.
skulach@head.genebee.msu.su

The review summarizes the present state of our knowledge concerning alternative
functions of mitochondria, namely energy conservation in forms of protonic
potential and ATP, thermoregulatory energy dissipation as heat, production of
useful substances, decomposition of harmful substances, control of cellular
processes. The recent progress in understanding of some mitochondrion-linked
pathologies is described. The role of reactive oxygen species in these processes
is stressed. Possible mechanisms of programmed death of mitochondrion
(mitoptosis), cell (apoptosis) and organism (phenoptosis) are considered. A
concept is put forward assuming that mitoptosis is involved in some types of
apoptosis whereas apoptosis can be a part of a phenoptotic cascade. It is
hypothesized that septic shock, as well as the stress-induced brain and heart
ischemic diseases and cancer, exemplify mechanisms of phenoptosis purifying
population, community of organisms or kin from dangerous or useless individuals.

Publication Types:
Review
Review, Tutorial

PMID: 10626278 [PubMed - indexed for MEDLINE]

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#3 Mark Hamalainen

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Posted 22 July 2005 - 05:14 PM

Two advantages to allotopic expression I can think of immediately that would probably overcome any advantage to mitoptosis:

1. The mutation rate is as much as 10^5 times lower in the nucleus
2. Eliminates the potential for Aubrey's Selection of the Slowest, or a vicious cycle of mitoDNA damage.

I'll have to read more about what exactly is meant by mitoptosis before I can give a full response. As far as I'm aware mitochondria are only turned over by autophagy, so it seems that mitoptosis may be a misleading term.

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#4 eternaltraveler

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Posted 23 July 2005 - 12:10 AM

Very interesting. The obvious strategy this suggests is to work at making mitopotosis better as opposed to moving mito genes to the nucleus.

Search the animal and plant kingdoms for the mitos that kill themselves most effectively in the right circumstances, and work on finding the genes that cause that and get those genes into our mitos.

Are there any effective methods of transferring genetic material into mitos?

Perhaps it might be easier.

#5

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Posted 23 July 2005 - 12:43 AM

Nice to see you're dreaming about this stuff, Wolfram. I envy you - I think dreaming is probably one of the best ways of tapping into the brain's problem solving mode (or it means you are highly focused on a single topic - good either way). Now back to your theory, you're suggesting that the reason there is still some DNA propagated and expressed from mitochondria is that there is a selective advantage in retaining mitochondrial DNA. From your theory, this selective advantage is one that provides redundancy in mitochondrial DNA, is that right?

#6 John Schloendorn

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Posted 23 July 2005 - 04:43 AM

With mito genes in the mito there is a possibility to kill mutated mitos

While with mito genes in the nucleus there would be no mutated mitos in the first place... (And if there were, then all of them would be mutated in the same way and the cell should not continue to produce ROS, but rather die from energy depletion and that is much better than to stick around and mutate its way.) This is after all why we think most former mito genes were moved to the nucleus. What needs to be explained here is why most genes were moved, but some were not. I guess this cannot be explained without referring to specific differences between the genes or gene products that were moved and those that were not.

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#7

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Posted 23 July 2005 - 09:41 AM

What needs to be explained here is why most genes were moved, but some were not.


There is the much talked about hydrophobicity issue - some proteins cannot be be transported into mitochondria due to their hydrophobic nature. There is also a theory which links the need for some proteins to be directly synthesized within mitochondria for regulatory purposes by being responsive to the mitochondrial internal oxidative state.

#8 olaf.larsson

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Posted 23 July 2005 - 02:52 PM

What needs to be explained here is why most genes were moved, but some were not.



The genes which did not move are according to my idea those which in mutated state contribute to ROS production; genes for mito complex proteins. The benefit to be able to delete the mutated genes is greater then the benefit of having them in the nucleus in a less mutagenic environment but not possible to delete. But I can ofcourse not proof my claim in any way.

Edited by wolfram, 23 July 2005 - 03:08 PM.


#9 olaf.larsson

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Posted 24 July 2005 - 03:53 PM

Well there are ofcourse nuclear genes that could increase ROS production if mutated for example mito-dna-pol. This fact undermines my idea.

Edited by wolfram, 25 July 2005 - 12:07 AM.


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#10 Mark Hamalainen

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Posted 24 July 2005 - 07:37 PM

Has everybody read... http://www.gen.cam.a...s/HH-CDH-PP.pdf ?

#11 olaf.larsson

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Posted 25 July 2005 - 01:23 AM

Yes I have heard of of the hydrophobicity theory it sounds suspect to me. If you look what genes there are in the mitos you see that there are genes of a special kind; ribosomal parts and mito complex proteins. Mito complexes have to be to some extent hydrophobic since they should be in the mitomembrane but there are other nucleus encoded mito proteins which are hydrophobic as well.

#12 Mark Hamalainen

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Posted 25 July 2005 - 01:56 AM

Read the whole paper, it discusses those issues.

The ribosomal parts are all tRNA's and they have to be there in order for the mtDNA to be translated. There are evolutionary explanations for why the protein encoding genes remain.

It seems to me that rather than just talk and talk about allotopic expression it should just be done! All the debate will be redundant once the experiment is performed.

#13 Hypermere

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Posted 01 August 2005 - 08:56 PM

Mitos were bacteria from the start. Let's go with allotropic expression and get it done. I thought of this myself months ago, like I did think of telomere repair about two months before I read the first article in the papers about it, back in the 90's. It is just common sense.

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#14 apocalypse

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Posted 03 August 2005 - 06:10 PM

What I've been thinking about this problem, is that if I understood the recent finding(accum of mut. in mitos leads to increased probability of cell death and not to ever increasing ROS production) correctly and it pans out to be true, then it may be that the reason the dna in mitos remains there may be in order to cause an intra-organism selective pressure.

By keeping such there the cell is probably more likely to devastate its own energy production and likely die sooner than it would if such where in the nucleus and it was producing mass ROS. The cells with optimum energy production efficiency would've a survival advantage, since their mtdna would be in better condition and aid in their survival and proliferation, these should also've less ndna damage. It'd also help keep cells with the least dna dmg in the event of some stress/toxin/etc since mtdna would most likely be dmg'ed more easily and compromise survival.

The rate of mut. in mitos might cause tissue regen demand overtime to reach the point where it ovewhelms, surpassing the ability of s-cells pools(given that, IIRC, their rate of tel-regen's limited.) to meet such, and causing degen. to accum.




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