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.
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.
- C.-h. O. Davis, K.-Y. Kim, E. A. Bushong, E. A. Mills, D. Boassa, T. Shih, M. Kinebuchi, S. Phan, Y. Zhou, N. A. Bihlmeyer, J. V. Nguyen, Y. Jin, M. H. Ellisman, N. Marsh-Armstrong. Transcellular degradation of axonal mitochondria. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1404651111
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