WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome, 2023 Hwang et al

Hoopoe

Hoopoe

Senior Member (Voting Rights)
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How is the WAVE3 gene connected to the mitochondria? The amount of the gene product is raised in ME/CFS patients, and that then influences the mitochondria somehow?

It seems like more and more researchers are interested in the mitochondria (& looking at muscle function / muscle biopsies) now in ME.. I’m glad that this avenue is being seriously looked at.
 
lunarainbows said:
How is the WAVE3 gene connected to the mitochondria?
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My understanding is that the link to mitochondria is autophagy (degradation of damaged cellular components) and maybe also organization of the mitochondrial network. It also has various other roles.

But this is a complicated topic and I may be misunderstanding. I'll have to read more. It's possible that the NIH knows something that we don't.

PS:

On further reading, a picture emerges of WAVE3 being part of one of several protein complexes that physically attach mitochondria to the endoplasmatic reticulum. This would also allow mitochondria and the ER to communicate with each other. This has been studied in cancer.
 
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Braganca said:
He clarifies that gene product was discovered to be raised in the ME cohort of the NIH intramural study which will be published by 2023.
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Wasn't the numbers of patients recruited to this study tiny i.e. around 35 over 5 years?
If it was as low as that wouldn't finding a significant gene product in such a tiny cohort be highly unlikely?
Sorry may be talking nonsense but I really don't trust Nath or Walitt.
 
@John Mac If my memory serves right, the investigators had issued an update to the participants in early 2020 noting that they had found evidence of mitochondrial dysfunction with the Seahorse assay. The number of patients is indeed too low to pinpoint a specific gene, but their results may point towards it possibly having a role in ME/CFS.

Edit: it is the expression of the gene that is upregulated here; this is not the same as identifying variants of the gene (which is the goal of a GWAS study). I don’t know whether assessing upregulation reliably requires as many patients as for a GWAS, i.e. at least 10.000 patients.
 
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Increased expression of this protein seems hard to interpret because it's involved in so many different things. But that the NIH is doing a mitochondrial study led by a cancer researcher suggests that they might be thinking that the interaction between WAVE3 and mitochondria is the most promising area. There also is some discussion of developing drugs that target WAVE3 to treat cancer. Maybe that's the kind of drug trials Dr Nath is expecting?
 
A bit more information on what the WAVE3 gene does in the cell besides having something to do with mitochondria.

It's part of a protein family that is also involved in cell movement, which involves restructuring of the cytoskeleton. I'm not entirely sure but believe that cell adhesion and cadherins, Wnt signaling and ephrine-eph signaling are also involved in cell movement according and these have been found to be abnormal in ME/CFS in some studies. Maybe a coherent picture is finally starting to emerge?

https://www.sciencedirect.com/science/article/pii/S0092867411006520
 
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The discovery involves the gene WAVE3, which helps determine the shape of cells (their cytoskeleton). The amount of this gene product was altered (raised) in the ME/CFS cohort.
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Does the WAVE 3 gene have anything to due with the deformability of red blood cells?

[It's not helping my search that "WAVE 3" is also a television news station in Louisville Kentucky. :rolleyes: ]
 
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