Mitochondria metabolism sets the species-specific tempo of neuronal development

• 成果类型: Article
• 署名作者: Iwata, Ryohei; Casimir, Pierre; Erkol, Emir; Boubakar, Leila; Planque, Melanie; Lopez, Isabel M. Gallego; 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, Sebastien; Davie, Kristofer; Mazzone, Massimiliano; V. Gounko, Natalia; Aerts, Stein; Ghesquiere, Bart; Fendt, Sarah-Maria; Vanderhaeghen, Pierre
• 署名单位: Flanders Institute for Biotechnology (VIB); KU Leuven; KU Leuven; Universite Libre de Bruxelles; Flanders Institute for Biotechnology (VIB); KU Leuven; Flanders Institute for Biotechnology (VIB); Flanders Institute for Biotechnology (VIB); KU Leuven; University Hospital Leuven; Flanders Institute for Biotechnology (VIB); Flanders Institute for Biotechnology (VIB); KU Leuven; KU Leuven; University Hospital Leuven; KU Leuven; Flanders Institute for Biotechnology (VIB); KU Leuven; KU Leuven
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13334
• DOI: 10.1126/science.abn4705
• 发表日期: 2023-02-10
• 页码: 553-+
• 关键词: cell-metabolism; brain; inhibition; glycolysis; maturation; plasticity

摘要

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.