Satellite Glial Cell-to-Neuron Mitochondrial Transfer Protects Against Neuronal Dysfunction and Pain in Peripheral Neuropathy

Abstract

Peripheral neuropathy is a common and disabling disorder characterized by sensory dysfunction, axonal degeneration, and neuropathic pain, yet disease-modifying treatments remain limited. Mitochondrial dysfunction is increasingly recognized as a central contributor to diabetic and chemotherapy-induced neuropathies, but most studies have focused on mitochondria within sensory neurons themselves. Recent work by Xu et al. identifies satellite glial cells as active metabolic partners that transfer mitochondria to dorsal root ganglion neurons through MYO10-dependent tunneling nanotube-like structures. This glia-to-neuron mitochondrial transfer preserves neuronal bioenergetics, maintains axonal integrity, and alleviates pain-related hypersensitivity in experimental neuropathy models, with supporting evidence from human dorsal root ganglia. This highlight discusses how these findings reshape peripheral neuropathy as a disorder of impaired neuron-glia metabolic cooperation and place satellite glial cells at the center of mitochondrial homeostasis in sensory ganglia. We also discuss unresolved questions regarding activity-dependent transfer signals, sensory-neuron subtype specificity, disease breadth, and therapeutic translation. Understanding and harnessing intercellular mitochondrial transfer may open new strategies for restoring neuronal resilience and treating neuropathic pain.