Donated Mitochondria Help Alleviate Nerve Damage and Pain in Mice

Mitochondrial transfer from glial cells to neighboring sensory neurons reduced neuropathic pain in mice, indicating its therapeutic potential.

Fast-acting cells, such as sensory neurons, require a lot of energy to function, so they have a high demand for mitochondria. But how do these cells generate and maintain enough of these powerhouse organelles to sustain themselves?

Ru-Rong Ji, a pain researcher at Duke University, and his colleagues recently discovered that glial cells that surround sensory neurons play a critical role in this process: They transfer mitochondria to their neighbors.¹ When the researchers blocked this process in mice, the animals experienced more nerve damage and pain. These findings, published in Nature, highlight mitochondrial transfer as a possible solution for treating chronic pain in humans.

Researchers once thought that each cell is responsible for its own mitochondria supply, but mounting evidence suggests that the organelles can move between neighboring cells. Ji and his colleagues wondered if this was also the case for sensory neurons and their surrounding glial cells.

To address this question, the researchers co-cultured mice sensory neurons and glial cells and labeled their mitochondria with a dye (MitoTracker). They watched the two cell types interact under the microscope and observed that over 80 percent of neurons received mitochondria from glial cells via a few different mechanisms. Blocking endocytosis, the formation of gap junctions, and specialized structures called tunneling nanotubes (TNT) suppressed mitochondrial transfer.

Next, Ji and his colleagues investigated if their findings in cultured cells held true in live animals. They labeled the mitochondria of mice glial cells, and then they imaged the cells and their neighboring sensory neurons five and 10 days later. On the tenth day, 23 percent of neurons contained mitochondria from glial cells. Inhibiting endocytosis and TNT formation also significantly decreased mitochondrial transfer from glial cells to sensory neurons, aligning with the researchers’ in vitro data.

To further evaluate how applicable their results were to humans, Ji’s team analyzed human neurons and glial cells from healthy and diabetic donors (up to 50 percent of patients with diabetes experience nerve damage). There was less mitochondrial transfer between the glial cells and sensory neurons of patients with diabetes than their healthy counterparts. Furthermore, the introduction of healthy human donors’ glial cells—or mitochondria isolated from these cells—to diabetic mice alleviated their hypersensitivity to touch, a key symptom of neuropathic pain.

“By giving damaged nerves fresh mitochondria—or helping them make more of their own—we can reduce inflammation and support healing,” said Ji in a statement. “This approach has the potential to ease pain in a completely new way.”