Something New Found in Blood

[Wishful]

https://newatlas.com/biology/unexpected-new-component-discovered-bloodstream/

"Mitochondria are normally found inside cells, but the team has now discovered them floating around on their own in the bloodstream."

I expect the research teams will be checking to see if this is the 'something in the blood' involved with ME.

 

[Hip]

Amazing discovery. Here's the full paper.

I guess the big question now is what purpose these free-floating mitochondria might have. The paper says that mitochondria were recently discovered to translocate from one cell to the other. So maybe the mitochondria in the blood serve as a pool of readily available mitochondria, that can enter into cells should any cells need extra mitochondria to bolster their energy production.

 

[Wishful]

So maybe the mitochondria in the blood serve as a pool of readily available mitochondria, that can enter into cells, should any cells need extra mitochondria to bolster their energy production.

For some reason, my brain is conjuring up more interesting possibilities, such as evil pirate mitochondria, with eyepatches and wooden legs, swinging over to a target cell with blood-curdling screams, or zombie mitochondria, shuffling along, attacking good mitochondria. Just ignore me, I have ME...

There was also that discovery earlier about a separate lymph network (or something like that) that no one had noticed before. It makes me wonder what else is in our bodies that no one has noticed yet. That video about the basketball court where no one notices the gorilla-costumed guy walking across it comes to mind.

 

[junkcrap50]

From what I found online, mitochondria (1-10um) would be too large to be the "something in the blood" as it's much larger than exosomes (30-100nm)

 

[Pondering]

What an amazing discovery. Hard to believe it was missed up to now. The discovery seemed amazing enough that I went and double checked that the journal is peer reviewed (which it seems to be if I am reading it correctly).

From a layperson's perspective, this seems like a large number of them. "We estimate that there are between 200 000 and 3.7 million cell‐free intact mitochondria per mL of plasma "

 

[Rufous McKinney]

that can enter into cells should any cells need extra mitochondria to bolster their energy production.

Oh- nothing can go wrong with that little maneuver!

Wonder what the purpose of the vesicle...containing the mitochrondria is....thats part of the cell that made the mitochrondria's membrane I assume....so whe releasing a mitochondria, it comes in a package...are these membranes...selecting and allowing...messages in and out to these mitochondria...?

 

[Hip]

From a layperson's perspective, this seems like a large number of them. "We estimate that there are between 200 000 and 3.7 million cell‐free intact mitochondria per mL of plasma "

It's actually not that many if you consider how many cells there are per ml of blood, which is around 5 million. And the number of cells per one ml of tissue is much higher, about 460 million by my calculation. The number of mitochondria in each cell varies widely, but can be up to 1000 to 2000 mitochondria.

 

[sb4]

Perhaps this could explain why very high doses of supplements / b vitamins have an effect. They don't need transporters into cells, they just effect mitos in the blood? Perhaps the thing in the blood with ME is effecting these blood mitos which is causing blood flow issues / sticky blood / POTS?

 

[lenora]

Perhaps this could explain why very high doses of supplements / b vitamins have an effect. They don't need transporters into cells, they just effect mitos in the blood? Perhaps the thing in the blood with ME is effecting these blood mitos which is causing blood flow issues / sticky blood / POTS?

Very interesting. A friend's father was a scientist studying mitochondria about 22 yrs. ago. Her Sr. Science project was about it and a few yrs. later the father of a friend studying jvenile diabetes won an award at Southwestn and, as I recall, the Nobel Prize. He later died of brain cancer, and I have a goddchild with Juvenile Diabetes. Her mother testified before Congress and would pass info along to me. A great loss when these people go. The Mitochondria Researcher is still hard at work, though. Who knows where breakthroughs can come from? We absolutely have to support our Researchers....no question about it.

My friend with the JD daughter (now way over 30 yrs. old) now has MS herself and is paying $80,000/yr. for her drug to stay alive. Yes, you read that right. I thought, and thought that research would head our way but it never did. If we want it done, we have to do it ourselves. I can see the other group is trying to reach me. Off now...have a fairly decent evening/night everyone. I know, I know!! Yours, Lenora

 

[ZeroGravitas]

Oh cool, I came here to see if there was discussion of this after seeing this tweet (of this article and the already linked paper). And it seems you all jumped in a couple weeks ago.

So maybe the mitochondria in the blood serve as a pool of readily available mitochondria, that can enter into cells should any cells need extra mitochondria to bolster their energy production.

Right, the paper says that inter-cell mito transfer can be used "as a means to rescue injured tissues". So maybe in part the free-floating mitos can do that...?

I wonder what differences might be seen, with free mitos, in us pwME/CFS? Will we see fewer in our blood? E.g. if our bodies have greater demand for this donar function.

Or e.g. if "clearance and degradation [of these free-floating mitos] occurs principally by phagocytosis" and we see enhanced phagocyte activity in pwME/CFS(?), then a deficiency?

Conversely, they note mitos role as "systemic messengers", so it seems most likely that their role will be immune modulation, in some regard. E.g. sensitive detection of infection/chemical stressors in the blood?

I'm very eager to know what Naviaux's take will be on this, with regard to innate immunity and his cell danager response (and healing cycle) framework of understanding!

It's actually not that many

Yeah, the paper describes their concentration as "dilute", in regards to not having previously discovered their existence here. So, even though they are alive and "respiratory competent", it seems unlikely they'd be contributing to energy production in this context (right?).

But what if their energy production capability is impaired in a similar way to that of whole cells from serum? And this can be measured reliably? The paper mentions their use of a "Seahorse XF‐96 extracellular flux analyzer", a device I've heard about repeatedly from our researchers. So it seems certain that this is something that could be fairly quickly investigated in pwME/CFS (verses controls). So hoping to hear from Ron, too (Janet replied to that tweet to say she'd passed it along to him).

 

[Hip]

So, even though they are alive and "respiratory competent", it seems unlikely they'd be contributing to energy production in this context (right?).

I don't think these free mitochondria would be able to generate much energy, as mitochondria cannot generate energy from glucose and oxygen on their own; mitochondria need the assistance of glycolysis, a process which is found in the cytosol of the cell. Mitochondria alone can generate energy from fats and oxygen though.

I think it will take some time to figure out the actual purpose of these free mitochondria.

 

[sb4]

@Hip Couldn't the free mitochondria use serum lactate or pyruvate for energy also?

 

[lenora]

Thanks, Zeroe Gratvitas and Hip.....An interesting "discussion" between the two of you. Is it possible for me to get a link to the research. Not that i don't trust you, what I don't trust is my poor beleaguered brain to sort anything out at this time. It will take a few readings in order for me to make sense of any of it. Not my age, I'm actually "on top" of my game given that I'm 73, but this recent battle will take time to come back from and I want to be a worthy person contributing the right things to this group. Thanks!! And have a good evening, gentlemen! Yours, Lenora.

 

[Hip]

@Hip Couldn't the free mitochondria use serum lactate or pyruvate for energy also?

That's true, I guess these mitochondria could make use of the pyruvate in the blood to create energy.

Inside cells, glycolysis inputs glucose, and outputs ATP energy plus pyruvate. That pyruvate can then be taken up by the mitochondria and combined with oxygen (burnt) to make more ATP energy.


But there are so few of these free mitochondria floating in the blood that even if they were making ATP energy, it would be a very low amount.

I calculated (see below) that in the heart muscle, there is a density of around 50 billion mitochondria per cm3. Whereas in the blood, the paper estimates a density of around 1 million mitochondria per cm3. So the density of mitochondria in the blood is over 10,000 times less than the density of mitochondria in the blood.

Spoiler: Heart mitochondria calc

Total number of cells in heart muscle = 3 billion
Number of mitochondria in each heart muscle cell = 5000
Volume of heart = around 300 cm3 = 300 ml

So in the heart, there are roughly 3 billion x 5000 / 300 = 50 billion mitochondria per cm3.

 

[lenora]

OK, gentlemen, I'm leaving this ball in your court. I'm clearly in no mental capacity to undertake this at the moment, although I would like a clearer understanding of what's occurring and why? That's me, I'll read and connect the dots, but I have to admit this is clearly out of my court at the moment. Please don't think people like me aren't interested. You're obviously brighter than I am, and that's a good thing. All minds bring something to the table.

Please talk to "We the people, also, at times." I'm sure there are others who want to understand what's occurring in different fields of research...of that I have no doubt. I have a support and only yesterday received a lengthy letter from a woman from NJ that I befriended back in the 1990's thanking me for propelling her forward. I actually did get burned out & had to put distance between myself and the people with my illnesses. Funny, how so many of us go through that. In the meantime, I always heavily supported research as I firmly believe the answers to all our problems lie in it and we'll gain momentum faster and faster over the years, mos. and even days. You young ones have every chance of getting back to your lives and I'll support you in any manner I can; as does my husband. It's just that we're spread rather thin...this is the 4th group I'm invested in. I like the double/more particularly triple giving days. I don't know if you org. has them or not. Yours, Lenora

 

[sb4]

@Hip The heart contains the most mito per cell though. There is a much greater volume of blood the heart cells, what if the flux of mito going in and out of blood is relatively high. This could make a significant impact I guess. Unless the mitos in blood are destined to stay in blood.

I read a theory recently that all glucose oxidation goes through lactate and that (brain, and muscle) mitos can then use this for energy. The idea was that other cells could produce lactate and spill it over into the serum to provide energy for cells that need it. If this is true there would be ample amounts in blood.

 

[Hip]

Is it possible for me to get a link to the research.

The link is in the first post.

 

[Hip]

The heart contains the most mito per cell though.

Yes, the heart muscle cells have a lot of mitochondria, no doubt because this muscle is in constant use.


We can also look at this another way: the amount of ATP in the blood, and in the cells.

Google tells me that blood plasma ATP concentration is roughly 1000 nmol/L (nano moles per liter). Whereas cell ATP concentration is in the range of 1 to 10 mmol/L (milli moles per liter).

So the ATP concentration in the blood is around 1000 to 10,000 times less than the concentration found inside cells.

Though as you suggest, it could be that the flux of flowing blood supplies a reasonable amount of ATP to cells which might need it (depending on how efficiently ATP can cross the cell membrane).


But from this study, it seems the purpose of ATP in the blood may be for signaling purposes, rather than for energy supply:

Locovei et al reported ATP release from erythrocytes in response to low oxygen tension and osmotic stress, providing a luminal source of ATP, presumably to act on endothelial cell purinergic receptors to induce vasodilation

 

[Pyrrhus]

So the ATP concentration in the blood is around 1000 to 10,000 times less than the concentration found inside cells.

Though as you suggest, it could be that the flux of flowing blood supplies a reasonable amount of ATP to cells which might need it (depending on how efficiently ATP can cross the cell membrane).


But from this study, it seems the purpose of ATP in the blood may be for signaling purposes, rather than for energy

That's correct. ATP has a very different purpose inside the cell and outside the cell. Ideally, ATP is manufactured and used inside the cell, where it is used for energy. ATP is only released outside the cell in stress scenarios, where it is used to signal danger.

Thus, when a muscle cell is stressed, it may suffer a micro-tear, releasing ATP outside the cell. This ATP is then picked up by purinergic sensors on nociceptive neurons, leading to the familiar sensation of muscle soreness. (often incorrectly referred to as "lactic acid burn")

I suppose it's possible that extracellular mitochondria may also serve as danger signals, rather than as energy producers...

 

[percyval577]

ATP is only released outside the cell in stress scenarios, where it is used to signal danger. ... This ATP is then picked up by purinergic sensors on nociceptive neurons, leading to the familiar sensation of muscle soreness. ...

I suppose it's possible that extracellular mitochondria may also serve as danger signals, rather than as energy producers

This gives a pretty impressive picture.

They may produce and release ATP for two purposes 1) purinergic signaling, but they 2) could also help to provide rapidly growing new cells with ATP (if there is an import mechanism), who knows, maybe they even could get endocytosed (I don´t know how likely this may be).

Danger and possible wound healing, I would say.