MITOCHONDRIA AS TARGETS FOR THERAPEUTIC INTERVENTION IN MUSCLE CELL DEATH

Mitochondria are the power plants of eukaryotic cells. They transform the energy of foodstuffs into the chemical energy (ATP) that the cells require for their function. In order to perform their job, mitochondria also receive and send chemical and electrical signals that perfectly integrate into the network of intracellular regulation. Because of their critical position for cell survival, nature has also exploited mitochondria to remove senescent, transformed or no longer necessary cells in a process of cell suicide called apoptosis. When the proper signal arrives, mitochondria can stop producing ATP and/or release proteins that cause cell demise. Modern research in this field suggests that early apoptosis of muscle fibers may be one of the reasons why muscular dystrophies develop and evolve. Our Telethon program investigates the mechanisms through which mitochondria can favor, or even cause, cell death in murine models of muscular dystrophy. Because mitochondrial function can be investigated in muscle fibers from animals that harbor the genetic defect(s) prior to irreversible damage, mitochondrial derangements can be identified and drugs preventing these negative events can be developed and tested. This program is relevant because it might eventually lead to a novel pharmacological strategy to slow down the course and delay the onset of human muscular dystrophies.