The pyruvate generator is a common phenomenon in mitochondria from different rat and mouse brain regions.

The finding of the pyruvate generator ('mitochondrial gas pedal') arose from the observation that cytosolic Ca2+ accelerates glutamate-driven respiration. Here, we show that glutamate respiration of isolated rat brainstem mitochondria appears to be insensitive to extra-mitochondrial Ca2 +. This raises the question: Do these mitochondria lack a pyruvate generator, or is its detection masked? By reconstituting the complete malate-aspartate shuttle (MAS), we demonstrate that brainstem mitochondria possess a pyruvate generator, just like mitochondria from other brain regions. Direct measurement, however, is hindered by the high rate of Ca2+-insensitive glutamate utilization by glial mitochondria. We therefore conclude that the pyruvate generator is a universal mechanism in all tissues that contain a functional MAS and pyruvate-generating enzymes.