Impaired mitochondrial respiration promotes dendritic branching via the AMPK signaling pathway.
Functional neuronal circuits require a constant remodeling of their network composed of highly interconnected neurons. The plasticity of synapses and the shaping of elaborated dendritic branches are energy demanding and therefore depend on an efficient mitochondrial oxidative phosphorylation (OXPHOS). The spatial and functional regulations of dendritic patterning occur also after cell fate specification; however, the molecular mechanisms underlying this complex process remain elusive. Here, we exploit the changes in dendritic architecture in highly branched neurons as a result of aberrant mitochondrial activity. In sensory neurons of Caenorhabditis elegans, genetic manipulations of mitochondrial complex I subunits cause an unexpected outgrowth of dendritic arbors and ectopic structures. The increased number of dendritic branches is coordinated through a specific signaling cascade rather than as a simple consequence of oxidative stress. On the basis of genetic and pharmacological evidence, we show that OXPHOS deficiency promotes branching through the activation of the AMP-activated protein kinase AMPK and the downstream target phosphoinositide 3-kinase PI3K. Taken together, our findings describe a well-defined signaling pathway that regulates dendritic outgrowth in conditions of compromised OXPHOS and the resulting AMPK activation.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
A
A
Gioran
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
P
P
Nicotera
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
D
D
Bano
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D019069:Cell Respiration; D003712:Dendrites / Q000201:enzymology*; D042967:Electron Transport Complex I; D004789:Enzyme Activation; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D055372:AMP-Activated Protein Kinases; D042967:Electron Transport Complex I