Neural activity and CaMKII protect mitochondria from fragmentation in agingCaenorhabditis elegansneurons

Decline in mitochondrial morphology and function is a hallmark of neuronal aging. Here we report that progressive mitochondrial fragmentation is a common manifestation of agingCaenorhabditis elegansneurons and body wall muscles. We show that sensory-evoked activity was essential for maintaining neuronal mitochondrial morphology, and this activity-dependent mechanism required the Degenerin/ENaC sodium channel MEC-4, the L-type voltage-gated calcium channel EGL-19, and the Ca/calmodulin-dependent kinase II (CaMKII) UNC-43. Importantly, UNC-43 phosphorylated and inhibited the dynamin-related protein (DRP)-1, which was responsible for excessive mitochondrial fragmentation in neurons that lacked sensory-evoked activity. Moreover, enhanced activity in the aged neurons ameliorated mitochondrial fragmentation. These findings provide a detailed description of mitochondrial behavior in aging neurons and identify activity-dependent DRP-1 phosphorylation by CaMKII as a key mechanism in neuronal mitochondrial maintenance.