Direct exposure to N-methyl-d-aspartate alters mitochondrial function

• A previous study reported the detection of an NMDA-sensitive binding site on nervous system mitochondria.
• NMDA augmented mitochondrial ROS formation without altering membrane potential.
• NMDA attenuated cytochrome c release and delayed Ca2+-induced mitochondrial swelling.
• Activation of the NMDA-sensitive binding site may stabilize mitochondrial function.

N-methyl-d-aspartate (NMDA) receptors have long been known to be associated with the plasma membrane, providing a channel for the passage of extracellular Ca2+ into the cytosol during synaptic transmission. Recent results from our laboratory indicate that in addition to this classic location, an NMDA-sensitive site (NMDAm) may also exist within the inner mitochondrial membrane. We report direct exposure of mitochondrial to NMDA enhances the production of reactive oxygen species and attenuate ROS-induced cytochrome c release, all the while slowing the rate of Ca2+-induced mitochondrial swelling. Treatment with NMDA did not alter the mitochondrial membrane potential. The findings of this study lend further support for the existence of NMDAm and suggest that this site may serve to stabilize mitochondrial function.