A new study from the UK shows how genetic mutations linked to Parkinson's disease may play an important role in the death of brain cells by interfering with their natural process for getting rid of faulty mitochondria, the tiny powerhouses inside cells that are vital for effective cell functioning. The finding may offer new targets for effective drug treatments.

The researchers - from University College London, the University of Cambridge and the University of Sheffield - write about their findings in an August 11th online issue of Nature Neuroscience.

The paper describes how defects in the Parkinson's gene Fbxo7 disrupt the process of "mitophagy," the process cells use to eliminate faulty mitochondria.

Mitochondria are tiny powerplants inside cells that provide the energy cells need for all their essential tasks such as making proteins and sending and receiving signals. Their function is vital for energy-hungry nerve and brain cells.

If mitochondria malfunction, they can cause serious harm to cells, which normally dispose of them quickly by 'eating' them - which is essentially what mitophagy is.

Much of what we know about mitophagy in the brain has come about because of studying familial forms of Parkinson's disease.

For instance, two genes linked to inherited forms of the disease, PINK1 and Parkin, are now known to be key to mitophagy: PINK1 regulates mitochondrial quality control, and Parkin is involved in protein degradation.

A study published in 2010 showed how mutations of PINK1 and Parkin disrupt healthy mitchondria functioning, and suggests they play a role in causing Parkinson's disease.

In this latest study, the researchers show how important mitophagy is to Parkinson's disease, and how mutations in Fbxo7 interfere with the PINK1-Parkin pathway.

Co-lead author Dr Heike Laman from the University of Cambridge, explains the contribution the study makes to Parkinson's disease (PD) research:

"This research focuses the attention of the PD community on the importance of the proper maintenance of mitochondria for the health of neurons.

We are really only at the very beginning of this work, but perhaps we can use this information to enable earlier diagnosis for Parkinson's disease patients or design therapies aimed at supporting mitochondrial health."

The researchers believe drugs that target mitophagy could be a way forward for developing effective treatments for Parkinson's disease.

Co-author Dr Helene Plun-Favreau from the UCL Institute of Neurology, adds:

"What makes the study so robust is the confirmation of defective mitophagy in a number of different Parkinson's models, including cells of patients who carry a mutation in the Fbxo7 gene."

The study was part-funded by the Medical Research Council (MRC), where Professor Hugh Perry is chair of their board of neurosciences and mental health. He says the study raises some interesting questions about how brain cells die in Parkinson's disease, and answering these will be key to understanding how the disease progresses.

The work was also funded by the Wellcome Trust and The NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

Written by Catharine Paddock PhD