Cell-specific expression of key mitochondrial enzymes precludes OXPHOS in astrocytes of the adult human neocortex and hippocampal formation

The astrocyte-to-neuron lactate shuttle hypothesis entails that glycolytically derived pyruvate in astrocytes is converted to lactate instead of being catabolized in mitochondria. The mechanism of this metabolic rewiring is unclear. Here we show that astrocytes of the adult human neocortex and hippocampal formation do not express mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS) to a detectable degree, including cytochrome c and complex IV. Without OXPHOS, human brain astrocytes are bound to produce lactate to avoid interruption of glycolysis.