Neurons Get Their Neighbors To Take Out Their Trash

Some cells in the retina pass off worn out parts to supporting cells for disposal.

Biologists have long considered cells to function like self-cleaning ovens, chewing up and recycling their own worn out parts as needed. But a new study challenges that basic principle, showing that some nerve cells found in the eye pass off their old energy-producing factories to neighboring support cells to be “eaten.” The find, which may bear on the roots of glaucoma, also has implications for Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis (ALS) and other diseases that involve a buildup of “garbage” in brain cells.

The study was led by Nicholas Marsh-Armstrong, Ph.D., a research scientist at the Kennedy Krieger Institute and an associate professor in the Johns Hopkins University School of Medicine’s Solomon H. Snyder Department of Neuroscience, together with Mark H. Ellisman, Ph.D., a neuroscience professor at the University of California, San Diego. In a previous study, the two had seen hints that retinal ganglion cells, which transmit visual information from the eye to the brain, might be handing off bits of themselves to astrocytes, cells that surround and support the eye’s signal-transmitting neurons. They appeared to pass them to astrocytes at the optic nerve head, the beginning of the long tendril that connects retinal ganglion cells from the eye to the brain. Specifically, they suspected that the neuronal bits being passed on were mitochondria, which are known as the powerhouses of the cell.

The image shows a retinal ganglion cell.
Reconstruction of electron microscopy data showing part of a retinal ganglion cell (blue) in the optic nerve head of a normal, healthy mouse. Its two bulges are filled with mitochondria (red). The researchers believe this is one step in the process of shedding the mitochondria so that neighboring astrocytes can break them down. Credit UCSD.

To find out whether this was really the case, Marsh-Armstrong’s research group genetically modified mice so that they produced indicators that glowed in the presence of chewed up mitochondria. Ellisman’s group then used cutting-edge electron microscopy to reconstruct 3-D images of what was happening at the optic nerve head. The researchers saw that astrocytes were, indeed, breaking down large numbers of mitochondria from neighboring retinal ganglion cells.

“This was a very surprising study for us, because the findings go against the common understanding that each cell takes care of its own trash,” says Marsh-Armstrong. It is particularly interesting that the newly discovered process occurs at the optic nerve head, he notes, as that is the site thought to be at fault in glaucoma. He plans to investigate whether the mitochondria disposal process is relevant to this disease, the second leading cause of blindness worldwide.

But the implications of the results go beyond the optic nerve head, Marsh-Armstrong says, as a buildup of “garbage” inside cells causes neurodegenerative diseases such as Parkinson’s, Alzheimer’s and ALS. “By showing that this type of alternative disposal happens, we’ve opened up the door for others to investigate whether similar processes might be happening with other cell types and cellular parts other than mitochondria,” he says.

Notes about this neuroscience research

This study was funded by the National Eye Institute (grant numbers R01 EY022680 and R01 EY019960), a Catalyst for a Cure grant from the Glaucoma Research Foundation and the Melza M. and Frank Theodore Barr Foundation, the National Center for Research Resources (grant number 5P41RR004050), the National Institute on Drug Abuse’s Human Brain Project (grant number DA016602), the National Institute of General Medical Sciences (grant numbers 5R01GM82949, 5P41GM103412-25 and 5T32GM07814) and the National Science Foundation (grant number DGE-1232825).

Contact: Shawna Williams – Johns Hopkins Medicine
Source: Johns Hopkins Medicine press release
Image Source: The image is credited to UCSD and is adapted from the Johns Hopkins Medicine press release
Original Research: Abstract for “Transcellular degradation of axonal mitochondria” by Chung-ha O. Davis, Keun-Young Kim, Eric A. Bushong, Elizabeth A. Mills, Daniela Boassa, Tiffany Shih, Mira Kinebuchi, Sebastien Phan, Yi Zhou, Nathan A. Bihlmeyer, Judy V. Nguyen, Yunju Jin, Mark H. Ellisman, and Nicholas Marsh-Armstrong in PNAS. Published online June 16 2014 doi:10.1073/pnas.1404651111

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