Genetic diseases of mitochondrial shape: integrated approaches to understand pathogenesis and establish treatments

Dominant optic atrophy is a genetic disease characterized by progressive loss of sight, starting during early childhood. This is caused by the death of the retinal ganglion cells, the neurons transmitting the images from the eye to the brain. This death is painless and occurs at a steady pace over the years, ultimately leading to blindness. Thus, we think that it occurs by an exaggeration of the normal process of suicide, called apoptosis, that allows renovation of all the cells of our body. If we want to generate new drugs that block this degeneration, we need to understand the processes that lead to the death of these cells. Mitochondria, the “powerhouse” of the cells, are not only responsible for generating the energy that our cells need to live, but are also key players during apoptosis. When they become involved in cell death, their shape changes dramatically. Some proteins, called dynamins, control the shape of mitochondria and when they are damaged serious diseases leading to blindness ensue. In particular, one of these proteins, called OPA1, is affected in dominant optic atrophy. We intend to study how this protein is regulated, to elucidate its function in the life and the death of the retinal ganglion cells, to explore if it can be a target of drugs that interfere with the death of these cells and ultimately can stop the path to blindness.