Genetic mutations ruined mitochondria, the energy-producing organelles inside cells, inducing neurons in the brain's substantia nigra to perish or get impaired in Parkinson's disease, new study shows.The study from Children's Hospital Boston found 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.
Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' periphery in order to fuel the axons and dendrites that send and receive signals.
However, arresting this movement is equally important since it allows mitochondria to be quarantined and destroyed when they go bad, said senior investigator Thomas Schwarz, PhD, of Children's F.M. Kirby Neurobiology Centre.
"Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too. It's the equivalent of an environmental disaster in the cell," Schwarz explained.
Studying neurons from fruit flies, rats and mice, as well as cultured human cells, Schwarz and colleagues provided the most detailed understanding to date of the effects of the gene mutations, which encode the proteins Parkin and PINK1. hey demonstrated 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. The organelle, unable to move, can then be disposed of: The cell literally digests it.
But when either PINK1 or Parkin is mutated, this containment system fails, leaving the damaged mitochondria free to move about the cell, spewing toxic compounds and fusing to otherwise healthy mitochondria and introducing damaged components.
Findings appear in the November 11 issue of Cell.