Grant: Operating Grant

Mitochondria are bean-shaped organelles that evolved from the symbiotic relationship of aerobic bacteria living inside the primordial animal cell. They were discovered over 50 years ago as the power plant of the cell: primary energy-generating systems that converts sugars into ATP. In the past 10 years, however, the study of mitochondria in laboratories across the world has become very intense, mainly because mitochondria have been found to be also a major store of calcium and the gatekeepers of programmed cell death, a process that when activated can cause neurodegenerative diseases like Parkinson's and blindness, and when inhibited can cause cancer. But how mitochondria regulate so many and diverse cellular functions? Recent studies have shown that much of the way this organelle can do that is by changing its shape: becoming elongated like a "spaghetti", or fragmented in small units like "lentils", renders the mitochondrion competent to execute specific cellular programs, but not others. Since this breakthrough discovery, an increasing number of human diseases and metabolic disorders have been found to be caused by the inability of mitochondria to shift their shape in order to respond to the ever changing energetic and physiological needs of the cell. Our laboratory has pioneered some of the main aspects related to the regulation of these mitochondrial dynamics. Thus, the research program illustrated here starts from our previous discoveries to explore, next, how mitochondrial enzymes that degrade proteins that execute the "spaghetti-to-lentil" transition control the various functions of this unique organelle. This is necessary in order to discover which of the many still uncharacterized "mitochondrial diseases" are specifically caused by a deficit in the activity of these enzymes, so that we can designed therapeutics that can treat them.