XMRV and Mitochondria?

[Gerwyn]

Mitochondrial DNA (mtDNA) is the DNA located in organelles called mitochondria, structures within cells that convert the energy from food into a form that cells can use. Most other DNA present in eukaryotic organisms is found in the cell nucleus.

Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin,

Each mitochondrion is estimated to contain 2-10 mtDNA copies.

mtDNA is inherited from the mother (maternally inherited).

Mechanisms for this include simple dilution (an egg contains 100,000 to 1,000,000 mtDNA molecules, whereas a sperm contains only 100 to 1000), degradation of sperm mtDNA in the fertilized egg, and, at least in a few organisms, failure of sperm mtDNA to enter the egg. Whatever the mechanism, this single parent (uniparental) pattern of mtDNA inheritance is found in all mammals.

In sexual reproduction, mitochondria are normally inherited exclusively from the mother.

The mitochondria in mammalian sperm are usually destroyed by the egg cell after fertilization. Also, most mitochondria are present at the base of the sperm's tail, which is used for propelling the sperm cells. Sometimes the tail is lost during fertilization.


Mutations in mtDNA can in some cases cause maternally inherited diseases and some evidence suggests that they might be major contributors to the aging process and age-associated pathologies.[3



Virus infections are a major cause of mt DNA mutations see for example

http://www.nature.com/embor/journal/v8/n2/full/7400878.html


MuLV integrates into the mitochondrial genome causing nonsense mutations and forming non-functional repair proteins

XMRV is a MulV class gamma retrovirus

Gammaretroviruses are pathological when inserted into host DNA because of base deletions.the more deletions the more pathogenic.

XMRV has more deletion sequences than any other Gammaretrovirus by a country mile

 

[subtr4ct]

Hi Gerwyn -- Thanks as always for your insights. Are you saying that debilitating fatigue, via mitochondrial dysfunction, would be a natural symptom of XMRV infection?

 

[Frickly]

Thanks Gerwyn! I am amazed at all the research coming out. I really think we are headed in the right direction. :victory:

 

[lostinthedesert]

We need human vertical transmission studies and lab studies on human germ cells. Need to know if and how often this happens. Dear mom i wish i had stashed some of your blood. I do know i got a funky hla-dr haplotype from her but dont know how that relates to xmrv. Peace, S

 

[Gerwyn]

Hi Gerwyn -- Thanks as always for your insights. Are you saying that debilitating fatigue, via mitochondrial dysfunction, would be a natural symptom of XMRV infection?

directly or indirectly yes

 

[Gerwyn]

We need human vertical transmission studies and lab studies on human germ cells. Need to know if and how often this happens. Dear mom i wish i had stashed some of your blood. I do know i got a funky hla-dr haplotype from her but dont know how that relates to xmrv. Peace, S

i wonder of looking for mutations/insertions in maternal mitochondria might be the basis of a study?

 

[spindrift]

i wonder of looking for mutations/insertions in maternal mitochondria might be the basis of a study?

We have three generations of FM/CFS in our family. Maternal or dominant pattern. Hard to tell right now because none of the boys have
had children yet. A study like that would be interesting.

 

[FernRhizome]

the metabolic process that mitochondria are responsible for involves about 200 chemical steps. The steps are divided into five complexes and complex II involves exclusively nuclear DNA. The other steps involved mostly mitochondrial DNA, but also now they've discovered some nuclear genes are also involved in those steps. I have blood samples in a mitochondrial repository that is now looking at 1000 nuclear genes that are involved in mitochondrial function. This is all very new research, and very interesting. It's part of the MitoCarta project in Boston. So while it's true that mitochondrial DNA is inherited from the mother only, nuclear DNA from both parents are still involved. 10 years ago they didn't know this.~ Fern

 

[Gerwyn]

the metabolic process that mitochondria are responsible for involves about 200 chemical steps. The steps are divided into five complexes and complex two involve exclusively nuclear DNA. The other steps involved mostly mitochondrial DNA, but also now they've discovered some nuclear genes are also involved in those steps. I have blood samples and a mitochondrial repository that is now looking at 1000 nuclear genes that are involved in mitochondrial function. This is all very new research, and very interesting. It's part of them MitoCarta project in Boston. So while it's true that mitochondrial DNA is inherited from the mother nuclear genetics from both parents are still involved. 10 years ago they didn't know this.~ Fern

sure and it is interesting . i also find the work showing how small the mutations in mito dna have to be to exhert a collossal impact on mito output

 

[acer2000]

MuLV integrates into the mitochondrial genome causing nonsense mutations and forming non-functional repair proteins

XMRV is a MulV class gamma retrovirus

Gammaretroviruses are pathological when inserted into host DNA because of base deletions.the more deletions the more pathogenic.

XMRV has more deletion sequences than any other Gammaretrovirus by a country mile

So... what does this mean for XMRV infected people? Are our mitos toast once infected because from that point on they will have corrupted DNA? Or if the infection is brought to a halt, or eliminated, can the mitos resume normal function (and presumably reproduction)?

 

[FernRhizome]

That's the big question. Will anti-XMRV drugs make us better? Or is there going to be permanent damage. Wish we all knew. ~Fern

 

[jace]

So... what does this mean for XMRV infected people? Are our mitos toast once infected because from that point on they will have corrupted DNA? Or if the infection is brought to a halt, or eliminated, can the mitos resume normal function (and presumably reproduction)?

Whoa, acer, let us hope the second possibility turns out to be the case :worried:

 

[Gerwyn]

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

 

[Navid]

That's the big question. Will anti-XMRV drugs make us better? Or is there going to be permanent damage. Wish we all knew. ~Fern

ok i'm no gerwyn...but i am sooo thankful for gerwyn and ppl with that type of scientific understanding and the ability to break it down for ppl like me:Retro smile:

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...

in those moments (mine never last a whole day)....i start making grand plans for what i'm going to do...big trip, part time work that i find meaningful, ski, rock-climb, bicycle, swim.....maybe march in an anti-war demonstration:Sign Peace: (i wanted to use this emoticon)

it's amazing how quickly my mind goes back to it's old self even with a small window of feeling good.

 

[jewel]

I'm hoping you are right, Lisag. I know exactly what you are describing. When I am feeling well, the world seems to open up. Yes, even a half-day of feeling well, and all the plans start to revive.... Another way this disease is different than depression or an IAIYH explanation. Why would one have "sickness beliefs and behaviors" only to drop them from time to time. Actually, I've often thought I suffer from denial, not depression, because for years every time I felt well, I thought I was well for good. (Ok, I've derailed this thread off the topic of mitos... I hope they are sturdy enough to recover...)

 

[MaryAnn]

Mayo Clinic has a Mitochondrial Disease Biobank (I hope this link works) @http://mayoresearch.mayo.edu/mitochondrial-disease-biobank/intro.cfm

Maybe they will add ME/CFS if XMRV and its damage to mito check out. Below is a quote from their intro page...I hope there is not an issue with copyrights when pasting.

"Mitochondrial Disease Biobank Introduction

The Mitochondrial Disease Biobank was established at Mayo Clinic in 2009. Our mission is to collect blood and tissue samples from patients with known mitochondrial diseases from around the world; and aid the advancement of mitochondrial medical research and medicine.

Approximately 1000 children per year in the U.S. are born with some form of mitochondrial disease. For the majority of patients, their mitochondrial disorder is an inherited condition. However, an uncertain percentage of patients acquire symptoms due to other factors, including exposure to mitochondrial toxins and aging.

Mitochondrial Medicine is a new and rapidly developing medical subspecialty. Even though conditions with an underlying mitochondrial cause were noted as far back as the late 1800's, it was only in 1959 that the first patient was diagnosed with a mitochondrial disorder. In 1963, researchers discovered that mitochrondria have their own DNA or “blueprint” (mtDNA), which is different than the nuclear DNA (nDNA) found in a cell’s nucleus, and this discovery has aided the expansion of mitochondrial genetics and medicine.

Today, mitochondrial cytopathies include over 40 different disease entities that have individual genetic features. The common factor among these diseases is that the mitochrondria are unable to completely burn food and oxygen in order to generate energy, which is essential for normal cell function.

Using samples collected by the Mitochondrial Biobank, researchers will learn more about a group of diseases collectively known as mitochrondrial disorders, which include:

Alpers’ progressive sclerosing poliodystrophy
Leber hereditary optic neuroretinopathy
Barth syndrome
Leigh and Leigh-like Syndrome
Chronic progressive external ophthalmoplegia
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
Dominant optic atrophy
Myoclonic epilepsy associated with ragged-red fibers (MERRF)
Friedreich’s Ataxia
Neuropathy, ataxia, and retinitis pigmentosa (NARP)
Hereditary paragangliom
Pearson syndrome
Hereditary spastic paraplegia
Wolfram syndrome
Kearns-Sayre syndrome
Our common goal is to advance the understanding of mitochondrial disease and rapidly translate our discoveries into better patient care."

 

[lansbergen]

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 do. It does not only feel good but at those moments my body reacts like nothing is wrong. Pitty it just last a short time. It takes me by suprise en it disappears in a blink. I am still astonished at it every time it happens.

 

[Gerwyn]

yes that is a real puzzle and i get that too.this is why i think of variable gene regulation effects trasposition and so on

 

[acer2000]

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"? :-/

 

[Navid]

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"? :-/

and if xmrv causes prostate cancer....why don't those ppl feel as exhausted as we cfid's pts do...until they are near the end of life?