Researchers from the Stanford School of Medicine have unraveled the mitochondrial mechanisms involved in Parkinson’s disease as part of a study that will be published Aug. 15 in Human Molecular Genetics.
Parkinson’s is a movement disorder and a neurodegenerative disease that results from the loss of structure and function of the neurons. Associate professor of pathology Bingwei Lu, a co-author of the study, said that previous research found a link between mitochondrial dynamics and the disease.
He joined mammalian neurobiologist Wendou Yu, a postdoctoral scholar in pathology, to complete the study, which examined two genes that are linked to controlling mitochondrial function, PINK1/Parkin.
“This dynamic morphology change is important for mitochondrial function,” Lu said. “We call morphology change fission and fusion, meaning the mitochondria can be made to produce to smaller units or can fuse to make longer units. We found that PINK1/Parkin specifically affects this mitochondrial fission or fusion process.”
“This study showed that PINK1/Parkin, the Parkinson’s-disease-causing genes, play an evolutionarily conserved role in regulating mitochondrial morphology through this fission/fusions process,” he added.
In previous work with fruit flies, Lu found that PINK1/Parkin influences mitochondrial dynamics. He wanted to pursue this study in order to see if what he found in his fruit fly research could be applied to other organisms.
“[Fruit flies] are a kind of lower organism, but it’s a very powerful genetic system, so we obtained a lot of information about how PINK1/Parkin worked,” he said.
Previous research with mammalian cells gave inconclusive results, so Lu set out to resolve some of the controversy.
“My interest is to see whether what we found in fruit flies is relevant in mammals and eventually relevant in human patients,” he said.
PINK1/Pathway and their pathways were examined in cultures of rodent hippocampal and dopaminergic neurons. A loss of dopaminergic neurons is specifically linked to Parkinson’s. Previous studies along the same lines did not use neuron cell cultures but rapidly dividing cell lines, which are unlike the neurons that are affected by Parkinson’s disease.
“Cell lines are like cancer cells,” Yu said. “They are different from neurons, because neurons are post-mitotic cells. They cannot divide. The cancer cells are very actively dividing, so they are different. Hippocampal neurons cannot do that.”
Yu has a more personal reason for studying neurodegenerative diseases, having connections to several people who have had them.
“The U.S. baby boomers are starting to retire,” Yu said.
“The people with Parkinson’s disease and Alzheimer’s disease will be increasing in the next 10 years. That’s why I study the neurodegenerative disease,” he added.
The researchers said the results of this study could potentially influence the way Parkinson’s is treated.
“Now we know the mitochondrial fission/fusion process is very important to PINK1/Parkin function, so if we can use drugs to manipulate the fission/fusion process, maybe it can be used to treat Parkinson’s patients that are directly involved with PINK/Parkin1 dysfunction,” Lu said.
Lu’s next step will be to study the disease with a closer relation to humans.
“What we used are rat neurons,” he said. “These are much closer to human cells than the fruit flies, but they are still not human cells; so the immediate step that we are interested in testing is whether in humans, PINK1/Parkin dysfunction causes similar effects on mitochondrial morphology or mitochondrial function.”