KEUN-YOUNG KIM, MARK ELLISMAN, NICHOLAS MARSH-ARMSTRONG
EDITOR'S CHOICE IN NEUROSCIENCE
C.O. Davis et al., “Transcellular degradation of axonal mitochondria,” PNAS, 111:9633-38, 2014.
Most cells clean up their own damaged mitochondria by transporting the organelles into lysosomes, where they are digested internally. Lysosomes are located in the cell body, so neurons with long axons were thought to shuttle far-off axonal mitochondria back to the cell bodies for disposal. Nicholas Marsh-Armstrong of Johns Hopkins University School of Medicine and colleagues observed that in mice, retinal glial cells called astrocytes, clustered around the head of the optic nerve, were constantly chomping up cellular parcels extruded by axons in the nerve, leading Marsh-Armstrong to wonder what the neurons might be exporting for degradation.
Marsh-Armstrong and his colleagues used 3-D and transmission electron microscopy to identify the organelles being shed as mitochondria. Axonal mitochondria tagged with a fluorescent transgene showed up within adjacent astrocytes and were apparently degraded there.
This “strange biology” may be a more efficient means for long axons to eliminate mitochondria, Marsh-Armstrong suggests, or it “may be a stress-related pathway to prevent oxidative damage.” Old mitochondria that linger inside neurons too long can injure cells by releasing reactive oxygen species (ROS) or immunogenic mitochondrial DNA. “If neuronal mitochondria were not properly degraded by astrocytes, it’s hard to imagine [the mitochondria] would not produce an inflammatory response,” he says.
The view ahead
Glial cells digesting neurons’ mitochondria is “surprising, but plausible,” says Don Mahad of the University of Edinburgh. If reproducible, the results may be relevant in disease. “In disorders where glia are damaged, such as multiple sclerosis, you might get axonal damage [because] glia are unable to process [the shed] mitochondria.”