Research news from Bhupesh Prusty

Can anyone explain what kind of extracellular signals would induce mitochondrial fission?

Also what does it mean that cells are doing a lot of mitochondrial fission, does it occur in response to an impairment in energy production?

 

He seems to think its a neurohormone thats doing the mitochondrial fission. Read some papers about ß-adrenergic signaling and mitos here. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297546/ So do we end up at autoimmune produced adrenergic stimuli again ?

 

Yes, Prusty became quite active on Twitter when the fundraiser began. Not too sure what to think of it. As long as his findings are solid, I don't necessarily see him providing insights into his research as a "wrong" way to boost the fundraiser. But it's irresponsible of him if he knows his findings are not very meaningful, both for the financial aspect (donations coming straight from the pockets of people with ME) and for creating false hopes.

Now the NIH and Solve ME/CFS think that his research is serious, so I wouldn't think the latter holds. Still, we don't know that until his findings are peer-reviewed, published & replicated. So I'll go with cautious optimism, personally.

And let's hope his Twitter account doesn't go dead now that the fundraiser has met its goal.

EDIT: actually, Prusty has been interacting on Twitter ~1x a week quite consistently even before the fundraiser began.

I couldn't find a tweet from Prusty saying that the factor he's identified is a neurohormone. Is that something he has alluded to in the past? His presentation at the NIH conference in April 2019 made no mention of that either.

He only tweeted that the factor is not a viral particle but a cellular component.

 

In case it helps

https://en.wikipedia.org/wiki/Mitochondrial_fission

So fission isn't necessarily bad.

As an example of that,
Physiological Mitochondrial Fragmentation Is a Normal Cardiac Adaptation to Increased Energy Demand.

https://www.ncbi.nlm.nih.gov/pubmed/29233845

 

I'm not sure what mito fission tells us in the context of ME. Relevant:

https://twitter.com/user/status/1233714429914755073


https://twitter.com/user/status/1233527116785946630

 

A speculation based on my very limited layman's understanding might be that if we have something in our blood that limits energy production, this might spur the mitochondria to attempt to compensate by splitting (with the 'intention' of increasing the number of functioning mitochondria). However, if the same, or perhaps even an additional, "something in the blood" impairs that process somehow, all we might end up with is fragmented mitochondria that are less efficient - until, perhaps, the something in the blood is cleared or becomes less concentrated.

 

@cassava7 we contacted him this week.

 

I am very severe, I have been in contact with Dr. Bhupesh, my family has met him. Being a realist, having a little understanding of the complexity of the issue at hand and especially the knowledge that there is so much we do not understand about mitochondria I doubt this will be a breakthrough soon. But what I definitely do not doubt is the sincerity of Dr. Bhupesh and his work to try to get closer to an answer! He has a very refreshing approach to this disease and its patients, we need more of that. We need more crowdfunding for researchers like him, we need to invest more in ourselves and our future, this will only increase the chance of get big money like only NIH is capable of spending. Stop buying that bullshit supplement, give that money to research instead. I am also a big fan of OMF, but they seem to go down the wrong road with their metabolic trap centric funding, also I find them relatively uncreative when it comes to collecting money and informing patients about what they are doing precisely.

 

what do you mean, i just last week got an email telling me that OMF employed a PhD student with a big DONATE NOW button at the bottom for the big news. Whats next, Fluge and Melle got a new facility manager - DONATE NOW. (sarcasm off)

 

@butter sorry you are so bad. Thank you for telling us a but about Bhupesh. He certainly comes across as sincere to me, good to hear that people who've had 'non-twitter' contact with him think so too.
I think he's made it clear there is no 'quick win' in his tweets, but it's nice to have a little hope.

 

Thanks for letting us know

Looking at this list of neurohormones, issues with releasing and neurohypophysial hormones can arguably be ruled out. Otherwise blood tests would show them in most people with ME.

This leaves us with two interesting categories:

- adrenomedullary hormones: epinephrine, norepinephrine, dopamine, which are secreted by the adrenal glands. Could be involved in cardiovascular issues in ME, including orthostatic intolerance?
- enteric neurohormones: serotonin and histamine secreted by enterochromaffin cells in the gut.

Given that the microbiome is known to be affected (OMF's Severely Ill Patient Study), that serotonin is a product of tryptophan metabolism (metabolic trap theory) and that food intolerances and MCAS are common comorbidities of ME, this second category sounds relevant.

All neurohormones have a small molecular mass, so would this concur with Ron Davis' point that the factor(s) in the blood is/are not large molecules?

Sorry if there's a lot of nonsensical babble here.

 

@cassava7 i suggest watching this video

https://www.youtube.com/watch?v=w4s0uNy8Q2g

its about a guy who had the most severe fatigue and recovered after they surgically removed both adrenal glands. Nothing else worked for him. No medication. Not even the removal of one gland. Both needed to go.

 

I remember reading CNN's piece on his story (https://edition.cnn.com/2019/07/27/health/doug-lindsay-invented-surgery-trnd/index.html). Adrenal dysfunction is a major problem, but is there any previous study or data that would point towards it in ME?

 

@cassava7 nothing clear yet, but if he gets in this state of deep fatigue, and with the studies i have seen, i think the mitochondrial fission is coming from the adrenergic system. Not saying this is important for Cfs. The mitochondrial fission seen in Cfs could be just a side effect and not really important for the systems in the end. But im just guessing here like everyone else.

 

Increase in Dynamin-1-like protein (which is involved in fission) and inhibition of the proteins that lead to fusion, namely mitofusion 1 and 2.
https://en.wikipedia.org/wiki/DNM1L
https://en.wikipedia.org/wiki/MFN1
https://en.wikipedia.org/wiki/MFN2 (which are quite similar to a yeast enzyme involved in yeast budding)

Increased energetic demand. The separated mitochondria have increased surface area which can increase their energetic output, though increases their vulnerability to damage by reactive oxygen species and the like.

I suspect it is a positive adaptation, rather than a perpetuating factor.

https://www.sciencedirect.com/science/article/pii/S0005272816300858
They go on to state that MFN2 activity is important "in regulating the mevalonate biosynthesis pathway, which, in turn, is required to maintain mitochondrial coenzyme Q levels".

Notably CoQ10 levels are lower during viral infection and lower CoQ10 levels lead to greater resistance to viruses (but may increase susceptibility to bacterial infection)...

 

I assume that there was some indication of a problem with the functioning of the adrenal system - levels of hormones excreted or increased sensitivity to the hormone.

Jonas Bergquist found Pregnenolone to be significantly lower in people with ME [OMF funded study - https://let-me.be/e107_files/downloads/the_me_global_chronicle_-_30_-_20181222.pdf].

 

as I always expected... I haven't ever donated blood and I'll never do it

 

If the coming paper from Dr. Prusty has profound and lasting mitochondrial news, we need to get SS31/Elamipretide to patients to try it out as fast as possible imo. I have high hopes here because its stops mitochondrial fission. Im looking for it for ages now but besides shady china alibaba deals its waiting for an FDA approved med.

 

Is it extracellular? In one of his tweets, when asked if the factor is a viral particle, Prusty says "No, it's a cellular component."

That sounds more like Dynamin-related protein 1 (Drp1). [As mentioned by @Snow Leopard above.]


I don't know if it's relevant, but I found this paper on mitochondrial fission and fusion which suggests that fission can be used to dispose of a badly damaged part of a mitochondrion, while fusion may be employed to "rescue" a more viable mitochondrion by combining it with a healthier one - the result being a larger but somewhat less healthy mitochondrion.

It may be erroneous to think of mitochondrial fission in terms of a dividing cell that produces two identical copies. At least some of the time, fission may just be a way of getting rid of a part of a mitochondrion that might otherwise spread damage to the rest of it.

 

Facebook post from @Simon M

Code:

https://www.facebook.com/topmecfsresearch/posts/907217086399909

Do we know the results of a healthy cell in control serum incubated for 24 hours? Is it still different to the healthy cell incubated with 'extract of patient'?