2. Academic Validation
  3. Mitochondrial transfer from glia to neurons protects against peripheral neuropathy

Mitochondrial transfer from glia to neurons protects against peripheral neuropathy

  • Nature. 2026 Feb;650(8103):951-960. doi: 10.1038/s41586-025-09896-x.
Jing Xu 1,  Yize Li 1,  Charles Novak 1 2,  Min Lee 3,  Zihan Yan 4,  Sangsu Bang 1,  Aidan McGinnis 1,  Sharat Chandra 1,  Vivian Zhang 1,  Wei He 1,  Terry Lechler 3 5,  Maria Pia Rodriguez Salazar 3,  Cagla Eroglu 3 4 6 7 8,  Matthew L Becker 9 10,  Dmitry Velmeshev 4,  Richard E Cheney 11,  Ru-Rong Ji 12 13 14 15 16
Affiliations

Affiliations

  • 1 Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
  • 2 Department of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.
  • 3 Department of Cell Biology, Duke University Medical Center, Durham, NC, USA.
  • 4 Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
  • 5 Department of Dermatology, Duke University Medical Center, Durham, NC, USA.
  • 6 Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA.
  • 7 Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
  • 8 Duke Institute of Brain Sciences, Duke University, Durham, NC, USA.
  • 9 Department of Chemistry, Duke University, Durham, NC, USA.
  • 10 Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.
  • 11 Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 12 Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA. [email protected].
  • 13 Department of Cell Biology, Duke University Medical Center, Durham, NC, USA. [email protected].
  • 14 Department of Neurobiology, Duke University Medical Center, Durham, NC, USA. [email protected].
  • 15 Duke Institute of Brain Sciences, Duke University, Durham, NC, USA. [email protected].
  • 16 Department of Integrative Immunology, Duke University Medical Center, Durham, NC, USA. [email protected].
PMID: 41501451 DOI: 10.1038/s41586-025-09896-x
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.

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