An early step in Parkinson's disease: Problems with mitochondria

Feb 14, 2011

For the last several years, neurologists have been probing a connection between Parkinson's disease and problems with mitochondria, the miniature power plants of the cell.

Toxins that mimic Parkinson's effects act specifically to poison mitochondria, and mitochondria appear to be damaged in the brain cells that are endangered in the disease. But one unresolved question has been: are mitochondria simply the vulnerable "canaries in the coal mine" or is their deterioration a key step on the way to neurodegeneration?

Now researchers at Emory University School of Medicine have found that a protein called MEF2D, which helps withstand stress and toxins, also plays an unexpected role inside mitochondria. MEF2D's ability to keep mitochondria well tuned appears to be especially sensitive to impairment in Parkinson's disease, the research team found.

The results will be published online in the .

"Our data suggest that problems with MEF2D in mitochondria could represent one of the earlier steps in the progress of the disease," says senior author Zixu Mao, PhD, associate professor of pharmacology and neurology at Emory University School of Medicine. Postdoctoral researcher Hua She, PhD, was the first author.

The Emory team showed that MEF2D binds one particular mitochondrial gene, ND6, which is necessary for assembly of complex I. Complex I begins the electron transport process that is necessary for mitochondria to function.

Mitochondria are thought to have evolved from bacteria that once lived independently, but were engulfed and harnessed by a primitive cell millions of years ago. Mao and his colleagues found an example of how this symbiosis has extended to having proteins like MEF2D turn on genes inside mitochondria.

"Our findings make a convincing and very intriguing case that dysregulation of contributes to Parkinson's," Mao says.

Genes in the nucleus (that is, outside mitochondria) now encode most of the proteins that go into mitochondria. However, mitochondria still make a few of their own proteins, such as ND6.

In addition to showing how MEF2D functions in mitochondria, the team showed that toxins such as MPTP and the natural pesticide rotenone, which interfere with complex I and bring on Parkinson's in animals, also block MEF2D from working in mitochondria.

Mao's laboratory's previous research found that in Parkinson's, MEF2D levels are increased in the cell because of defects in a recycling process called autophagy. Now, they show that in the brains of Parkinson's patients, even when MEF2D levels are increased in the cell as a whole, they are reduced in mitochondria.

Because disruptions in have been linked to other neurodegenerative diseases and heart disease as well, Mao says probing MEF2D's involvement in those disease processes may yield new insights.

Explore further: Adolescent lifestyle not strongly tied to later muscular pain

More information: H. She, Q. Yang, K. Shepherd, Y. Smith, G. Miller, C. Testa and Z. Mao. Direct regulation of complex I by mitochondrial MEF2D is disrupted in a mouse model of Parkinson disease and in human patients. J. Clin. Invest. 121, (2011)

Related Stories

Toxicity mechanism identified for Parkinson's disease

Jan 02, 2009

Neurologists have observed for decades that Lewy bodies, clumps of aggregated proteins inside cells, appear in the brains of patients with Parkinson's disease and other neurodegenerative diseases.

New insight into Parkinson's disease

Apr 19, 2010

New research provides crucial insight into the pathogenic mechanisms of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The study appears in the April 19 issue of the Journal of Cell Biology.

Recommended for you

Philippines confirms second MERS case (Update)

15 hours ago

A foreigner who flew to the Philippines from the Middle East has become the second confirmed case of MERS in the country, the health department said Monday, as a deadly outbreak in South Korea spreads alarm across Asia.

Immigrant children given adult dose of hepatitis A vaccine

Jul 04, 2015

About 250 immigrant children were given an adult dose of a hepatitis A vaccine at a Texas detention facility where they were being held with their mothers, according to U.S. Immigration and Customs Enforcement officials.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.