Mitochondrial Dysfunction Induces Sarm1-Dependent Cell Death in Sensory Neurons

• DOI: 10.1523/jneurosci.0877-14.2014
• Publication Date: 2014-07-09T16:29:17Z
• Authors: D. W. Summers; A. DiAntonio; J. Milbrandt
• Keywords: Wallerian degeneration

Mitochondrial dysfunction is the underlying cause of many neurological disorders, including peripheral neuropathies. Mitochondria rely on a proton gradient to generate ATP and interfering with electron transport chain function can lead deleterious accumulation reactive oxygen species (ROS). Notably, loss mitochondrial potential precedes cellular demise in several programmed cell destruction pathways, axons undergoing Wallerian degeneration. Here, we demonstrate that depolarization triggers axon degeneration death primary mouse sensory neurons. These degenerative events are not blocked by inhibitors canonical pathways such as apoptosis, necroptosis, parthanatos. Instead, axodestructive factor Sarm1 required for this death. In absence Sarm1, poison CCCP still induces mitochondria, depletion, calcium influx, ROS, yet blocked. The survival these neurons despite ROS indicates acts downstream generation. Indeed, protects their from prolonged exposure ROS. Therefore, functions induce neuronal during oxidative stress. findings highlight central role novel form term sarmoptosis.