Mitochondria metabolism sets the species-specific tempo of neuronal development

Neuronal development in the human cerebral cortex is considerably prolonged compared with that of other mammals. We explored whether mitochondria influence the species-specific timing of cortical neuron maturation. By comparing human and mouse cortical neuronal maturation at high temporal and cell resolution, we found a slower mitochondria development in human cortical neurons compared with that in the mouse, together with lower mitochondria metabolic activity, particularly that of oxidative phosphorylation. Stimulation of mitochondria metabolism in human neurons resulted in accelerated development in vitro and in vivo, leading to maturation of cells weeks ahead of time, whereas its inhibition in mouse neurons led to decreased rates of maturation. Mitochondria are thus important regulators of the pace of neuronal development underlying human-specific brain neoteny.

Automated summary

Compared with other mammals, the development of neuronal in the human cerebral cortex takes longer. We investigated the impact of mitochondria on the species-specific timing of cortical neuron maturation. Through comparing the maturation of human and mouse cortical neurons, we found that the mitochondria development in human cortical neurons was slower, accompanied by lower mitochondria metabolic activity, especially oxidative phosphorylation. Stimulating mitochondria metabolism in human neurons accelerated their development in vitro and in vivo, enabling them to mature weeks ahead of time, while inhibiting mitochondria in mouse neurons resulted in decreased rates of maturation. Therefore, mitochondria play a crucial role in regulating the pace of neuronal development underlying human-specific brain neoteny.