The scientists also used a method that allowed them to generate larger-than-normal mitochondria, making them easier to see under a microscope. Ken Nakamura (left), Huihui Li (center), and Zak Doric (right) identified a process involving mitochondria that may be critical in protecting against neurodegeneration in Parkinson’s disease. “Getting that technique up and running was quite a challenge.” “We had to develop a new way of tracking individual mitochondria over long periods of time, almost a full day,” says Zak Doric, a graduate student at Gladstone and UC San Francisco (UCSF) and co-first author of the new study. In the new study published in the journal Science Advances, Nakamura’s group followed mitochondria inside living neurons and examined how PINK1 and Parkin affected their fate.īut mitochondria are small and they move inside cells, frequently fusing with each other or splitting in two, which makes them difficult to track. Indeed, neurons have unusually high energy needs and their mitochondria are much more resistant to degradation by Parkin than those in other cell types. While the role of PINK1 and Parkin in mitophagy has been heavily studied in many cell types, it has been unclear whether these proteins act the same way in neurons-the type of brain cells that die in Parkinson’s disease. Mutations in these same proteins also cause hereditary forms of Parkinson’s disease. In most cells, damaged mitochondria are decomposed in a process known as mitophagy, which is initiated by two proteins, PINK1 and Parkin. “It suggests that mitochondrial recycling is critical to maintaining healthy mitochondria, and disruptions to this process can contribute to neurodegeneration.” Breaking Down Damaged Mitochondria “This work gives us unprecedented insight into mitochondria’s life cycle and how they are recycled by key proteins that, when mutated, cause Parkinson’s disease,” says Gladstone Associate Investigator Ken Nakamura, MD, PhD, senior author of the new study. They showed that genes associated with Parkinson’s disease play key roles in this process. Now, researchers at Gladstone Institutes have taken a closer look at the life cycle of energy-generating cellular power plants-called mitochondria- inside brain cells, and how they might be recycled. Scientists have long known that living cells are master recyclers, constantly breaking down old parts and building them back up into new molecular machines.
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