Linking mitochondria metabolism, developmental timing, and human brain evolution.

Changes in developmental timing are an important factor of evolution in organ shape and function. This is particularly striking for human brain development, which, compared with other mammals, is considerably prolonged at the level of the cerebral cortex, resulting in brain neoteny. Here, we review recent findings that indicate that mitochondria and metabolism contribute to species differences in the tempo of cortical neuron development. Mitochondria display species-specific developmental timeline and metabolic activity patterns that are highly correlated with the speed of neuron maturation. Enhancing mitochondrial activity in human cortical neurons results in their accelerated maturation, while its reduction leads to decreased maturation rates in mouse neurons. Together with other global and gene-specific mechanisms, mitochondria thus act as a cellular hourglass of neuronal developmental tempo and may thereby contribute to species-specific features of human brain ontogeny.