Mitochondria metabolism sets the species-specific tempo of neuronal development
Open accessAbstract
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.
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Mitochondria metabolism and epigenetic remodeling regulate the species-specific tempo of human CPN maturation.
“While mitochondria metabolism and epigenetic remodeling were recently shown to regulate the species-specific tempo of human CPN maturation,21,22,23”
From Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition (2024) · cites this paper as [21]
The Discussion states that mitochondrial metabolic activity sets the species-specific tempo of cortical neuron development. It does not establish that epigenetic remodeling regulates that tempo: it says the extent of epigenetic changes remains undetermined and identifies chromatin remodeling as a possible additional mechanism. (LLM, conf=0.88)
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- Authors
- Iwata, R., Casimir, P., Erkol, E., Boubakar, L., Planque, M., Gallego López, I. M., Ditkowska, M., Gaspariunaite, V., Beckers, S., Remans, D., Vints, K., Vandekeere, A., Poovathingal, S., Bird, M., Vlaeminck, I., Creemers, E., Wierda, K., Corthout, N., Vermeersch, P., Carpentier, S., Davie, K., Mazzone, M., Gounko, N. V., Aerts, S., Ghesquière, B., Fendt, S.-M., & Vanderhaeghen, P.
- Affiliations
- Université Libre de Bruxelles (BE)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- VIB-KU Leuven Center for Cancer Biology (BE)
- VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium.
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- Corresponding author
- Iwata, Ryohei
- Casimir, Pierre
- Vanderhaeghen, Pierre
- ORCID
- 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
- Venue
- Science
- Published
- 2023-02-10
- Volume
- 379
- Issue
- 6632
- Pages
- eabn4705-eabn4705
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4318263660
- Cited by
- 312
- References
- 56
- Citations by year
- 2026: 85 · 2025: 89 · 2024: 94 · 2023: 43 · 2022: 1
- FWCI
- 36.25
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- Fonds Wetenschappelijk Onderzoek (1176821N)
- KU Leuven
- Fonds Baillet Latour
- H2020 European Research Council (771486)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mitochondrial metabolism, neuronal development, human cerebral cortex, oxidative phosphorylation, species differences, human-mouse comparison
- MeSH terms
- Animals, Cerebral Cortex, Energy Metabolism, Humans, Mitochondria, Neurons, Mice, Neurogenesis
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