Parkinson’s researchers at Columbia University Medical Center have found that a flaw in the way cells discard defective mitochondria may hold the secret to what causes the death of neurons in Parkinson’s disease.
Mitochondria first emerged as suspects in Parkinson’s in the 1980s after people taking street-produced opiates developed the disease. A contaminant in the drugs was later found to attack and damage mitochondria, structures inside the cell that produce all the cells’ energy.
But since then researchers have been unable to determine how mitochondria may be involved in other cases of Parkinson’s.
An investigation of two genes known to cause the disease has now provided a clue, according to a new paper published by researchers at Columbia, Cornell, and Johns Hopkins in the Proceedings of the National Academy of Sciences
The study found that Parkinson’s-causing mutations in the two genes prevent cells from sensing and removing damaged mitochondria, which then pile up inside the cells.
Accumulation of damaged mitochrondria, shown above,
inside the brain’s neurons may lead to Parkinson’s disease.
“In the long term, this buildup of defective mitochondria impairs the functions of neurons and ultimately leads to their deaths,” says the study’s lead author, Serge Przedborski, PhD, professor of neurology and pathology & cell biology.
The buildup occurs, the study found, if there is a mutation in one of two genes called PINK1 and Parkin. The two normally work together to alert the cell to the defective mitochondria. PINK1 senses the injury, while Parkin sends the damaged mitochondrion to be destroyed by autophagy, a process that breaks down and recycles cellular components.
“This physiological machinery may play a key role in maintaining a pool of healthy mitochondria in cells, including neurons,” Dr. Przedborski says.
Though PINK1 and Parkin mutations cause only a few percent of the 50,000 new cases of Parkinson’s disease diagnosed in the U.S. each year, Dr. Przedborski says that faulty mitochondrial disposal may also be involved in the majority of cases of with no known cause, but more research is needed.