The extracellular matrix integrates mitochondrial homeostasis, 2024, Zhang et al.

SNT Gatchaman

SNT Gatchaman

Senior Member (Voting Rights)
Staff member
The extracellular matrix integrates mitochondrial homeostasis
Hanlin Zhang; C. Kimberly Tsui; Gilberto Garcia; Larry K. Joe; Haolun Wu; Ayane Maruichi; Wudi Fan; Sentibel Pandovski; Peter H. Yoon; Brant M. Webster; Jenni Durieux; Phillip A. Frankino; Ryo Higuchi-Sanabria; Andrew Dillin

SUMMARY
Cellular homeostasis is intricately influenced by stimuli from the microenvironment, including signaling molecules, metabolites, and pathogens. Functioning as a signaling hub within the cell, mitochondria integrate information from various intracellular compartments to regulate cellular signaling and metabolism. Multiple studies have shown that mitochondria may respond to various extracellular signaling events. However, it is less clear how changes in the extracellular matrix (ECM) can impact mitochondrial homeostasis to regulate animal physiology.

We find that ECM remodeling alters mitochondrial homeostasis in an evolutionarily conserved manner. Mechanistically, ECM remodeling triggers a TGF-β response to induce mitochondrial fission and the unfolded protein response of the mitochondria (UPRMT). At the organismal level, ECM remodeling promotes defense of animals against pathogens through enhanced mitochondrial stress responses. We postulate that this ECM-mitochondria crosstalk represents an ancient immune pathway, which detects infection- or mechanical-stress-induced ECM damage, thereby initiating adaptive mitochondria-based immune and metabolic responses.

HIGHLIGHTS

• Hyaluronan degradation in the ECM induces mitochondrial remodeling

• This ECM-to-mitochondria communication pathway is evolutionarily conserved

• The TGF-β signaling mediates the ECM-to-mitochondria communication

• ECM remodeling promotes immunity through the TGF-β and mitochondrial signaling

Link | PDF (Cell)
 
Of course, it’s the ECM. This might be one of the missing links we have been waiting for. For years, I have been looking out for research that could potentially explain the connection between the hEDS phenotype and ME/CFS (which is real; ask 10 MDs who have seen more than a few hundred ME patients, and they will all essentially tell you the same). Just read the abstract, though, lol.
 
Last edited:
Kitty said:
Is there an anti-graffiti team to scrub it off?
Click to expand...

Elastic fibres are associated with fibrillin fibres. These have repeating units that tie in to a TGF beta binding protein at regular intervals if I remember rightly. Elastin tends to stay put once laid down - which is why we go wrinkly with time - we do not refresh our elastin. I am not so sure about the fibrillin but I suspect that the pinboards of TGF beta binding protein stay put long term. TGF beta itself will then get put on to the pinboards and taken off. It will probably wash off in time anyway if not replaced.

But as far as I know rather little is known about what controls all this and rather little attention has been paid to it in disease. I wrote a review of ankylosing spondylitis in 2000 with Jim Archer and Paul Bowness where we pointed out the uncanny similarity between AS sites and Marfan syndrome (a fibrillin defect). Beyond that I haven't seen much discussion in relation to pathogenic mechanisms.
 
Jonathan Edwards said:
Of the cocoon that the cell occupies - the tissue matrix.
Click to expand...

Jonathan Edwards said:
That is just because they are all parroting two very weak papers by Peter Rowe and Hans Knoop - yes the very same biopsychosocial Hans Knoop we all love to disbelieve on every other count!!
Click to expand...

I doubt the MDs I have spoken to even know who that is, I go with the MDs on that one. Not all ME is hEDS, but there is an overrepresentation of the phenotype and those with the phenotype appear to be more severe according to many of the MDs I have spoken with.
 
Jonathan Edwards said:
Elastic fibres are associated with fibrillin fibres. These have repeating units that tie in to a TGF beta binding protein at regular intervals if I remember rightly. Elastin tends to stay put once laid down - which is why we go wrinkly with time - we do not refresh our elastin. I am not so sure about the fibrillin but I suspect that the pinboards of TGF beta binding protein stay put long term. TGF beta itself will then get put on to the pinboards and taken off. It will probably wash off in time anyway if not replaced.

But as far as I know rather little is known about what controls all this and rather little attention has been paid to it in disease. I wrote a review of ankylosing spondylitis in 2000 with Jim Archer and Paul Bowness where we pointed out the uncanny similarity between AS sites and Marfan syndrome (a fibrillin defect). Beyond that I haven't seen much discussion in relation to pathogenic mechanisms.
Click to expand...

The pinboards you are referring to, is there an accepted term for them? Any literature? Thank you!
 
butter. said:
I doubt the MDs I have spoken to even know who that is, I go with the MDs on that one. Not all ME is hEDS, but there is an overrepresentation of the phenotype and those with the phenotype appear to be more severe according to many of the MDs I have spoken with.
Click to expand...

The MDs won't know who wrote the papers because they are just parroting what others parrot - it is a meme. It goes round and round medical meetings. It sells private practice.

There is no evidence of over-representation of a hyper mobile phenotype that I know of. Doctors believe what they hear in cosy departmental meetings without asking for actual data. The only studies I know of that are properly populate based do not show a link to hypermobility or the other way around from hypermobility to chronic pain and fatigue.

Hypermobility is something doctors love to point out because it seems to explain the unexplainable. I worked with the guy who started all this in UK terms and there was never any science to it. I am afraid that it is a topic awash with bullshit.
 
butter. said:
The pinboards you are referring to, is there an accepted term for them? Any literature? Thank you!
Click to expand...

No, that is my pet metaphor for the current discussion.
There is a vast literature on TGF beta binding protein and matrix.
But as I have said, very little seems to have been written on clinical relevance other than my paper on Ankylosing Spondylitis with Archer and Bowness in 2000 in Immunology.
 
Jonathan Edwards said:
The MDs won't know who wrote the papers because they are just parroting what others parrot - it is a meme. It goes round and round medical meetings. It sells private practice.

There is no evidence of over-representation of a hyper mobile phenotype that I know of. Doctors believe what they hear in cosy departmental meetings without asking for actual data. The only studies I know of that are properly populate based do not show a link to hypermobility or the other way around from hypermobility to chronic pain and fatigue.

Hypermobility is something doctors love to point out because it seems to explain the unexplainable. I worked with the guy who started all this in UK terms and there was never any science to it. I am afraid that it is a topic awash with bullshit.
Click to expand...

I think your opinion on the topic is widely disseminated. :) Let me just add that hEDS is not exclusively about hypermobility.
 
Last edited:
Jonathan Edwards said:
Elastic fibres are associated with fibrillin fibres. These have repeating units that tie in to a TGF beta binding protein at regular intervals if I remember rightly. Elastin tends to stay put once laid down - which is why we go wrinkly with time - we do not refresh our elastin. I am not so sure about the fibrillin but I suspect that the pinboards of TGF beta binding protein stay put long term. TGF beta itself will then get put on to the pinboards and taken off. It will probably wash off in time anyway if not replaced.

But as far as I know rather little is known about what controls all this and rather little attention has been paid to it in disease. I wrote a review of ankylosing spondylitis in 2000 with Jim Archer and Paul Bowness where we pointed out the uncanny similarity between AS sites and Marfan syndrome (a fibrillin defect). Beyond that I haven't seen much discussion in relation to pathogenic mechanisms.
Click to expand...

Interesting re Marfans - my daughter seems to be a " not quite" , and her similarities seemed common in other teens with ME/CFS ; perhaps a genetic clue
 
Deanne NZ said:
@Amw66 Similar to my son with ME. The doctor who diagnosed hEDS described him as Marfanoid but not actual Marfan syndrome. I think it had more to do with him being very tall and his arm span was greater than his height.
Click to expand...

Yes -tall, long slim hands and feet, flat feet, crowded mouth with narrow palette
my daughter has always been as flexible as a brick , but knees and hips are problematic - hips in particular sublux
eyesight now terrible and getting worse - optician advised a couple of years ago that her optic nerve looked similar at 20 to someone in their 40s
but here rheumatology couldn't find anything of interest ( not bendy enough and " too brave" when being examined for tender points ) and suggested joining a gym....
 
Amw66 said:
Interesting re Marfans - my daughter seems to be a " not quite" , and her similarities seemed common in other teens with ME/CFS ; perhaps a genetic clue
Click to expand...

Something I learnt as a rheumatologist is that 'not-quite Marfan's' or what is often called Marfanoid has nothing whatever to do with Marfan's itself - which you either have or do not have. A Marfanoid body is well within the range of normality. The deformities of true Marfan's are quite specific.
 
You must log in or register to reply here.
Back
Top Bottom