Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons
- PMID: 26124107
- PMCID: PMC4507213
- DOI: 10.1073/pnas.1501831112
Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons
Abstract
Decline in mitochondrial morphology and function is a hallmark of neuronal aging. Here we report that progressive mitochondrial fragmentation is a common manifestation of aging Caenorhabditis elegans neurons 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.
Keywords: C. elegans; CaMKII; mitochondria; neural activity; neuronal aging.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
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