Mutations in Hereditary Parkinson’s Disease Disrupt System for Disposing of Damaged Mitochondria

Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's Hospital Boston now shows that genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. Findings appear in the November 11, 2011 issue of Cell. Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' peripheries in order to fuel the axons and dendrites that send and receive signals. However, arresting this movement is equally important, says senior investigator Dr. Thomas Schwarz, of Children's F.M. Kirby Neurobiology Center, because it allows mitochondria to be quarantined and destroyed when they go bad. "Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too," Dr. Schwarz says. "It's the equivalent of an environmental disaster in the cell." Studying neurons from fruit flies, rats, and mice, as well as cultured human cells, Dr. Schwarz and colleagues provide the most detailed understanding to date of the effects of the gene mutations, which encode the mutated forms of the proteins Parkin and PINK1. They demonstrate how these proteins interact with proteins responsible for mitochondrial movement -- in particular Miro, which literally hitches a molecular motor onto the organelle. Normally, when mitochondria go bad, PINK1 tags Miro to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion.
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