Mitochondrial N-methyl-D-aspartate receptor activation enhances bioenergetics by calcium-dependent and -Independent mechanisms

Our laboratory has demonstrated that functional N-methyl-D-aspartate-like receptors are present on neuronal mitochondria (NMDA(m)). This novel site gates the influx of Ca2+ and causes a several-fold increase in ATP levels. Although elevations in ATP in other cell types have been linked to increases in mitochondrial Ca2+, it has not been established whether the same holds true for calcium uptake via NMDA(m). In this study, we have investigated the effect of NMDA(m) activation on a variety of bioenergetic parameters. Our findings suggest that mitochondrial bioenergetics are not only modulated by NMDA(m) activation in a Ca2+-dependent but also in a Ca2+-independent manner.