Mutations in the Valosin containing protein (VCP) gene are the cause of various neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), a form of motor neuron disease, and a rare multisystem disease which affects muscle, bone and brain.
VCP is involved in a lot of different functions in cells. We know that VCP is important for dealing with damaged proteins and mitochondria. Our work looked at how mutations in VCP can be bad for mitochondria, the energy-producing engines of cells, and we found that these damaged mitochondria are less efficient, burning more nutrients but producing less energy. This decrease in energy makes cells more vulnerable, which could explain why mutations in the VCP gene lead to cells dying in the brain.
Another paper by a group of researchers based in America, published in the same issue of Neuron as ours, shows how in healthy people VCP helps to eliminate other damaged proteins and mitochondria whose accumulation is toxic interfering in the mitochondrial clearance pathway known as mitophagy. When VCP protein is deficient and cannot do its job properly it causes damaged mitochondria and protein aggregates to accumulate in cells. The accumulation of different types of protein could explain why a single mutation in the VCP gene can cause different neurological diseases. It is quite rare for this to happen, and understanding how and why VCP is linked to these different disorders will give us a powerful insight into how these diseases occur.
Our research points to a problem with power supply in motor neuron disease and the multisystem disease information which will help us to understand the common degenerative process in disorders of the brain and central nervous system.