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XMRV and Mitochondria?

G

Gerwyn

Guest
Or it could be that the one of the viral proteins is acting as a toxin that is inhibiting mitochondrial respiration I guess... I really have no basis to know if thats true, but it could be an alternative explanation for the fatigue. Or perhaps it disrupts the flow of oxygen from the blood into the tissues/mitos. I always found it puzzling that my O2 Saturation was in the upper 90s (sometimes 98-99%), yet my v.02max and Anaerobic threshold was 50% of what it should be for my age. It argues for the idea that the 02 is in my blood, but not getting used.

Its an interesting question, and one that hasn't been directly addressed by the paper authors. If XMRV is going to be the cause of a disease called "CFS" (and for good reason), how exactly does XMRV cause said "fatigue"? :-/

there are a number of ways that a gammaretrovirus could cause fatigue direct and indirect mito damage are just two possibilities
 

mermaid

Senior Member
Messages
714
Location
UK
"but i think we can recover because don't most of us have days, hours or even minutes where we sometimes feel normal....its often fleeting but it's my touchstone that recovery is still possible...my body still has the capacity to feel good..."

I had just one of those days this weekend. It felt like real euphoria, both a real physical and emotional energy (or is that just adrenalin). It almost felt spiritual, it being Easter Sunday and all that, but I was so thrilled to see the sunshine and longing to go out into the garden to do my gardening. I felt alive for the first time in ages and it lasted all day. I even went out in the early evening to a low energy event.

Back to normal on Monday unfortunately. Maybe I could market this feeling ... call it LP perhaps ....

Actually I am still feeling euphoric even today - something to do with the Spring perhaps, but I do have fatigue and muscle pain today though which I didn't have on Sunday.
 

thegodofpleasure

Player in a Greek Tragedy
Messages
207
Location
Matlock, Derbyshire, Uk
Mitochondria are affected but probably not irreversibly damaged (?)

Whilst I agree that the mitochondria are in some way involved, I doubt that they are being damaged directly by the virus (whether that be xmrv or any other)
My layman's logic for believing this are :
  1. xmrv appears to be present in relatively small numbers and is likely to be concentrated in certain tissue types (which is why it is proving so difficult to find)- presumably therefore not infecting the large numbers of cells that would need to be involved if the mitochondria were individually infected.
  2. the Krebs cycle ( http://en.wikipedia.org/wiki/Krebs_cycle) involves a multitude of steps (each one involving a specific enzyme and some very complex chemistry) and is therefore vulnerable to disruption by anything that could interfere with those chemical processes / ion channels and hence slow down ATP synthesis in the mitochondria - http://en.wikipedia.org/wiki/Mitochondrion
  3. For most sufferers, it seems that exhaustion is not permanent, but is (at least to some extent) recoverable. Surely that would not be the case if the mitochondria were permanently genetically damaged. As several contributors have already commented, a feature of this illness is that we are not permanently debilitated with a lack of energy, but we do suffer from post exertional problems.
    My own exprience is that I can exert myself (after being well rested) and perform to quite a good level - I can run around and Umpire a game of hockey for example and feel alright immediately afterwards, but will suffer a "crash" several hours later. Hence I don't think that the mitochondria are irreparably damaged, but somehow they (or rather the chemical processes involved in the Krebs Cycle) are inhibited as a widespread knock-on effect of the presence of a small amount of virus somewhere in the body (Lungs, cardio-vascular system, muscles ?) - could this be caused by a post-exertional "cytokine storm" as suggested by Drs Alan & Kathleen Light's excellent research ?
  4. We are repeatedly told that we can train our bodies to do more - and to a limited extent, I think that is true :eek: Whilst I take issue with the GET and CBT thing, in my own case I recognise that I can steadily improve my own circumstances (during the summer months) if I build up V slowly and stay within my own limits. Again, I don't think that would be the case if the mitos were totally screwed.

I know that I'm only speculating here, but I thought it was worth putting in my two-penny worth ;)

TGOP
 
G

Gerwyn

Guest
Whilst I agree that the mitochondria are in some way involved, I doubt that they are being damaged directly by the virus (whether that be xmrv or any other)
My layman's logic for believing this are :
  1. xmrv appears to be present in relatively small numbers and is likely to be concentrated in certain tissue types (which is why it is proving so difficult to find)- presumably therefore not infecting the large numbers of cells that would need to be involved if the mitochondria were individually infected.
  2. the Krebs cycle ( http://en.wikipedia.org/wiki/Krebs_cycle) involves a multitude of steps (each one involving a specific enzyme and some very complex chemistry) and is therefore vulnerable to disruption by anything that could interfere with those chemical processes / ion channels and hence slow down ATP synthesis in the mitochondria - http://en.wikipedia.org/wiki/Mitochondrion
  3. For most sufferers, it seems that exhaustion is not permanent, but is (at least to some extent) recoverable. Surely that would not be the case if the mitochondria were permanently genetically damaged. As several contributors have already commented, a feature of this illness is that we are not permanently debilitated with a lack of energy, but we do suffer from post exertional problems.
    My own exprience is that I can exert myself (after being well rested) and perform to quite a good level - I can run around and Umpire a game of hockey for example and feel alright immediately afterwards, but will suffer a "crash" several hours later. Hence I don't think that the mitochondria are irreparably damaged, but somehow they (or rather the chemical processes involved in the Krebs Cycle) are inhibited as a widespread knock-on effect of the presence of a small amount of virus somewhere in the body (Lungs, cardio-vascular system, muscles ?) - could this be caused by a post-exertional "cytokine storm" as suggested by Drs Alan & Kathleen Light's excellent research ?
  4. We are repeatedly told that we can train our bodies to do more - and to a limited extent, I think that is true :eek: Whilst I take issue with the GET and CBT thing, in my own case I recognise that I can steadily improve my own circumstances (during the summer months) if I build up V slowly and stay within my own limits. Again, I don't think that would be the case if the mitos were totally screwed.

I know that I'm only speculating here, but I thought it was worth putting in my two-penny worth ;)

TGOP

they are not totally screwed(love the term) just damaged and not functioning properly and cant replenish ATP at a rate that is required by demand.When the ATP usage exceeds the rate of replacement and reserves are used up the crash ensues.

The ATP levels build up again crash over. The amount of activity allowed and severity/duration of the crash are dependent on degree of damage.
 

oerganix

Senior Member
Messages
611
they are not totally screwed(love the term) just damaged and not functioning properly and cant replenish ATP at a rate that is required by demand.When the ATP usage exceeds the rate of replacement and reserves are used up the crash ensues.

The ATP levels build up again crash over. The amount of activity allowed and severity/duration of the crash are dependent on degree of damage.

So, Gerwyn and others, what do you think of the possibility of stem cell treatments, whether ME is caused by XMRV or not? Dr. Cheney has had some success stories with his patients doing this, but none, I think, are very far past the treatment so we don't know whether they relapse or not.
 
G

Gerwyn

Guest
So, Gerwyn and others, what do you think of the possibility of stem cell treatments, whether ME is caused by XMRV or not? Dr. Cheney has had some success stories with his patients doing this, but none, I think, are very far past the treatment so we don't know whether they relapse or not.

Hi Organix.
i have read a little about it.I,m not sure of the purpose or what damaged cells he is aiming at.will be very interesting to monitor progress
 

Hope123

Senior Member
Messages
1,266
Well I found the following two papers to be of interest. They are both available free on Pubmed so I don't know if people want the full-text in the library here or want to get it themselves. The first is an older paper with Susan Vernon and Bill Reeves about differential expression of some mitochondrial genes in CFS patients.

The second is a newer more technical paper I have yet to read entirely. I knew mitochondria were involved in energy production but I did not know they also played a major role in carefully programmed cell death = "apotosis". Cell death occurs all the time in our bodies and is a way to get rid of cancerous, non-functioning, infected, etc. cells the body does not want anymore. Since viruses depend on the cell machinery inside cells they infect to replicate and on cell death to release large bunches of new viruses, many, many viruses have proteins either stopping cell death (more time to replicate!) or promoting cell death (time to release viruses!).

These viruses often affect the mitochondria and I suppose as a byproduct disrupt other mitochondrial functions like energy production along the way. The long list in this article includes HIV and HTLV. It makes me wonder if this is also why people with influenza and hepatitis infections also feel tired (other than cytokine activation) and might have some version of PEM but on a shorter time scale (flu e.g.) or slightly different scale (hepatitis) but we don't hear about it as much because they are "recognized" illnesses and healthcare staff do not say push people to exercise when they have the flu.

1. Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus
Suzanne D Vernon1 , Toni Whistler1 , Barbara Cameron2 , Ian B Hickie3 , William C Reeves1 and Andrew Lloyd2

http://www.biomedcentral.com/1471-2334/6/15

2. PLoS Pathog. 2008 May 30;4(5):e1000018.

Viral control of mitochondrial apoptosis.
Galluzzi L, Brenner C, Morselli E, Touat Z, Kroemer G.

INSERM, U848, Villejuif, France.

Abstract
Throughout the process of pathogen-host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.

PMID: 18516228 [PubMed - indexed for MEDLINE]PMCID: PMC2376094Free PMC Article
 
B

bluebell

Guest
because for years every time I felt well, I thought I was well for good.

False wellness beliefs, I know them well. ;)

I belonged to a support group for parents of children with hypotonia; some of the kids were diagnosed with mitochondrial disorders. Most had so many problems that the parent's sigs (where people used to list symptoms and diagnoses) were literally a half page long.
 

hvs

Senior Member
Messages
292
I really dont know.My opinion is that oxidative damage could be repaired by the mitos themselves when the source is removed.DNA damage on the other hand may well be permanent

Remember that treadmill tests show or VO2 max to be in the tank; no aerobic metabolism working. Drs. Peterson, Klimas, Lerner et al return many people to normal or near normal often by going after secondary herpes family viral infections. We can get mitochondria working again.
 

natasa778

Senior Member
Messages
1,774
Change of subject, sort of

Alternative explanation for the fatigue

What if feelings of fatigue, incl post-excercise one, is not (entirely) linked to mito dysfunction, but rather (or also) a consequence of ion channelopathies in CFS?

As an example http://www.ionchannels.org/showabstract.php?pmid=2054740, also ryanodine receptors are being investigated for their role in fatigue (interestingly they are also closely linked to mito membrane channels).

Viruses are well known to take control of all cellular calcium regulating proteins (most/all of them use calcium for their own means, especially crucial in assembly stage), so it would be surprising to find XMRV does not do the same...
 

natasa778

Senior Member
Messages
1,774
Re ryanodine receptors, this could well be unrelated, but I thought I'd mention because intolerance to caffeine has been mentioned so often in CFS:


RyRs are activated by millimolar caffeine concentrations. High (greater than 5 mmol/L) caffeine concentrations cause a pronounced increase (from micromolar to picomolar) in the sensitivity of RyRs to Ca2+ in the presence of caffeine, such that basal Ca2+ concentrations become activatory. At low millimolar caffeine concentrations, the receptor opens in a quantal way, but has complicated behavior in terms of repeated use of caffeine or dependence on cytosolic or luminal calcium concentrations


http://en.wikipedia.org/wiki/Ryanodine_receptor
Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic reticulum, an essential step in muscle contraction....
 

Overstressed

Senior Member
Messages
406
Location
Belgium
[*]xmrv appears to be present in relatively small numbers and is likely to be concentrated in certain tissue types (which is why it is proving so difficult to find)- presumably therefore not infecting the large numbers of cells that would need to be involved if the mitochondria were individually infected.

I think that you mix things up - the reason why XMRV is so hard to detect, is mainly because it is almost not found in the blood plasma. In that sense it is very comparable to another, feared retrovirus, HTLV, which is also hardly found in the blood, but mainly in human cells. It replicates probably from cell to cell. However, it does not mean it is there in small numbers. It appears it does replicate slow, it does not mean it is there in small numbers. I think I read a study where they infected monkeys with XMRV, and after a few days it was spread all over, with many viruses found in the stomach and gut.

But if the damage to the mitochondria is permanent, I can not answer. Let's hope not.

Take care,
OS.