2 Citations
Our understanding of mitochondrial signaling in the nervous system has
been limited by the technical challenge of analyzing mitochondrial
function in vivo. In the transparent genetic model Caenorhabditis elegans,
we were able to manipulate and measure mitochondrial ROS (reactive oxygen
species) signaling of individual mitochondria as well as neuronal activity
of single neurons in vivo. Using this approach, we provide evidence
supporting a novel role for mitochondrial ROS signaling in dendrites of
excitatory glutamatergic C. elegans interneurons. Specifically, we show
that following neuronal activity, dendritic mitochondria take up calcium
(Ca2+) via the mitochondrial Ca2+ uniporter MCU-1 which results in an
upregulation of mitochondrial ROS production. We also observed that
mitochondria are positioned in close proximity to synaptic clusters of
GLR-1, the C. elegans ortholog of the AMPA subtype of glutamate receptors
that mediate neuronal excitation. We show that synaptic recruitment of
GLR-1 is upregulated when MCU-1 function is pharmacologically or
genetically impaired but is downregulated by mitoROS signaling. Thus,
signaling from postsynaptic mitochondria may regulate excitatory synapse
function to maintain neuronal homeostasis by preventing excitotoxicity and
energy depletion.