Mitochondrial transfer from glia to neurons protects against peripheral neuropathy, 2026, Xu et al

[Sly Saint]

Abstract
Primary sensory neurons in dorsal root ganglia (DRG) have long axons and a high demand for mitochondria, and mitochondrial dysfunction has been implicated in peripheral neuropathy after diabetes and chemotherapy1,2. However, the mechanisms by which primary sensory neurons maintain their mitochondrial supply remain unclear. Satellite glial cells (SGCs) in DRG encircle sensory neurons and regulate neuronal activity and pain3. Here we show that SGCs are capable of transferring mitochondria to DRG sensory neurons in vitro, ex vivo and in vivo by the formation of tunnelling nanotubes with SGC-derived myosin 10 (MYO10). Scanning and transmission electron microscopy revealed tunnelling nanotube-like ultrastructures between SGCs and sensory neurons in mouse and human DRG. Blockade of mitochondrial transfer in naive mice leads to nerve degeneration and neuropathic pain. Single-nucleus RNA sequencing and in situ hybridization revealed that MYO10 is highly expressed in human SGCs. Furthermore, SGCs from DRG of people with diabetes exhibit reduced MYO10 expression and mitochondrial transfer to neurons. Adoptive transfer of human SGCs into the mouse DRG provides MYO10-dependent protection against peripheral neuropathy. This study uncovers a previously unrecognized role of peripheral glia and provides insights into small fibre neuropathy in diabetes, offering new therapeutic strategies for the management of neuropathic pain.

Mitochondrial transfer from glia to neurons protects against peripheral neuropathy - Nature

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuropathy.

www.nature.com

see also

Replenishing mitochondria significantly reduces chronic nerve pain, research shows

For millions living with nerve pain, even a light touch can feel unbearable. Scientists have long suspected that damaged nerve cells falter because their energy factories known as mitochondria don't function properly.

Now research published in Nature suggests a way forward: supplying healthy mitochondria to struggling nerve cells.

Using human tissue and mouse models, researchers at Duke University School of Medicine found that replenishing mitochondria significantly reduced pain tied to diabetic neuropathy and chemotherapy-induced nerve damage. In some cases, the relief lasted up to 48 hours.

Instead of masking symptoms, the approach could fix what the team sees as the root problem - restoring the energy flow that keeps nerve cells healthy and resilient.

Replenishing mitochondria significantly reduces chronic nerve pain, research shows

For millions living with nerve pain, even a light touch can feel unbearable. Scientists have long suspected that damaged nerve cells falter because their energy factories known as mitochondria don't function properly.

www.news-medical.net

 

[Creekside]

That's the sort of "previously unrecognized" I think might be involved in ME. Researchers haven't found a biomarker because they haven't been looking in the right places for the right sort of abnormalities. I doubt that anyone has checked that sort of mitochondrial transfer in PWME (vs non-healthy controls).

Of course, ME might not be as simple as one factor being significantly abnormal. Two or more factors might deviate just slightly, with the total effect being significant.

 

[Eleanor]

I was getting interested in this until I read "In some cases, the relief lasted up to 48 hours." Oh well.

Still:

Mitochondrial transfer has been implicated in diverse diseases, including obesity36, stroke14, inflammatory pain20 and cancer37,38. Our study demonstrates that SGC-to-neuron mitochondrial transfer occurs under physiological conditions, and its dysregulation drives neuropathic pain in animal models of nerve injury, CIPN and DPN. Mitochondrial dysfunction, a hallmark of CIPN2 and DPN1, is associated with pain, tingling and paraesthesia39, along with IENF loss40. Our findings provide direct evidence that impaired mitochondrial transfer from SGCs to DRG neuronal cell bodies is sufficient to trigger IENF degeneration and neuropathic pain behaviours. Small fibre neuropathy is common in chronic pain conditions, including CIPN, DPN and fibromyalgia41, We found that SGC-derived mitochondrial transfer preferentially targets medium- and large-sized neurons, but not small nociceptors, providing mechanistic insights into small fibre neuropathy.

 

[Creekside]

I was getting interested in this until I read "In some cases, the relief lasted up to 48 hours." Oh well.

If it's a reliable effect, even for a short period, it could lead to understanding why it works, which could lead to understanding the mechanism that causes ME, which in turn could lead to a treatment. At present we have no track to follow, so any hint of the mechanism could be useful.

 

[Eleanor]

If it's a reliable effect, even for a short period, it could lead to understanding why it works, which could lead to understanding the mechanism that causes ME, which in turn could lead to a treatment. At present we have no track to follow, so any hint of the mechanism could be useful.

Yes, absolutely - especially as these particular nerves aren't only involved in pain sensation (which these researchers are focusing on) but also, if I understand rightly, in regulating heart rate and blood pressure, respiration, digestion, and more.

 

[Creekside]

It seems reasonable that individual variations in the responses of nerves and the spacial positions of nerves could explain the wide variation of symptoms and responses in PWME. Optic nerves that are unusually sensitive to this mitochondrial transfer (or some other little-understood mechanism) might lead to light sensitivity, while for another person, nerves that control gut function are unusually sensitive. That's the sort of body system that is difficult to monitor, thus the lack of biomarker found.