Iwata Ryohei, Casimir Pierre, Erkol Emir, Boubakar Leïla, Planque Mélanie, Gallego López Isabel M, Ditkowska Martyna, Gaspariunaite Vaiva, Beckers Sofie, Remans Daan, Vints Katlijn, Vandekeere Anke, Poovathingal Suresh, Bird Matthew, Vlaeminck Ine, Creemers Eline, Wierda Keimpe, Corthout Nikky, Vermeersch Pieter, Carpentier Sébastien, Davie Kristofer, Mazzone Massimiliano, Gounko Natalia V, Aerts Stein, Ghesquière Bart, Fendt Sarah-Maria, Vanderhaeghen Pierre
VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium.
KU Leuven, Department of Neurosciences & Leuven Brain Institute, 3000 Leuven, Belgium.
Science. 2023 Feb 10;379(6632):eabn4705. doi: 10.1126/science.abn4705.
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.
与其他哺乳动物相比,人类大脑皮质的神经元发育显著延长。我们探究了线粒体是否影响皮质神经元成熟的物种特异性时间。通过在高时间和细胞分辨率下比较人类和小鼠的皮质神经元成熟情况,我们发现与小鼠相比,人类皮质神经元的线粒体发育较慢,同时线粒体代谢活性较低,尤其是氧化磷酸化活性。刺激人类神经元中的线粒体代谢导致体外和体内发育加速,使细胞提前数周成熟,而抑制小鼠神经元中的线粒体代谢则导致成熟速率降低。因此,线粒体是人类特异性脑幼态持续背后神经元发育速度的重要调节因子。