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 Ca 2+ accelerates glutamate‐driven respiration. Here, we show that glutamate respiration of isolated rat brainstem mitochondria appears to be insensitive to extra‐mitochondrial Ca 2 + . 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 Ca 2+ ‐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.