Endogenous mitochondrial hydrogen peroxide regulates neurogenesis during cortical development
| Title: | Endogenous mitochondrial hydrogen peroxide regulates neurogenesis during cortical development |
|---|---|
| Authors: | Mengual, Regina; Bobo-Jiménez, Verónica; Rodríguez González, Cristina; Lapresa, Rebeca; García-Rodríguez, Darío; Jiménez-Blasco, Daniel; Cabiscol, Elisa; Ros, Joaquim; Delgado-Esteban, María; Bolaños, Juan P.; Almeida, Ángeles |
| Contributors: | Instituto de Salud Carlos III; European Commission; Junta de Castilla y León; Agencia Estatal de Investigación (España); Ministerio de Ciencia, Innovación y Universidades (España); Fundación la Caixa; European Research Council; Consejo Superior de Investigaciones Científicas https://ror.org/02gfc7t72 |
| Publisher Information: | Elsevier BV |
| Publication Year: | 2025 |
| Collection: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| Subject Terms: | Cortex development; Hydrogen peroxide; Mitochondria; Neural precursor cells; Neurogenesis |
| Description: | Reactive oxygen species (ROS), particularly superoxide anion (O2•-) and hydrogen peroxide (H2O2), originating from mitochondria, are increasingly recognized as critical mediators of physiological signaling and cellular function. While in the adult brain, mitochondrial ROS, specifically mitochondrial H2O2, modulate metabolism and sustains cognitive processes, their role in the developing cerebral cortex remains undefined. Here, we leverage a knock-in mouse model constitutively expressing mitochondrially targeted catalase (mCAT) to attenuate mitochondrial H2O2 levels and investigate their impact during cortical development. In neurosphere cultures derived from embryonic day 14.5 (E14.5) mCAT mice, reduced mitochondrial H2O2 altered glutathione redox homeostasis and glucose metabolism leading to suppressed progenitor cell proliferation, without compromising viability. In vivo, neural progenitor cell (NPC) proliferation, neuronal differentiation and cortical layering were disrupted starting at gestational day E15. Together, these data uncover a physiological role for mitochondrial hydrogen peroxide in orchestrating neural precursor proliferation and differentiation, ultimately influencing mammalian cerebral cortex formation. ; This work was funded by Instituto de Salud Carlos III, co-funded by the European Union, (PI21/00727, PI24/00810, RD24/0009/0005 to AA; CB16/10/00282 to JPB), and funded by the European Union - NextGeneration EU, Recovery and Resilience Facility (RD21/0006/0005, PMP22/00084 to AA), Junta de Castilla y León (CSI011P23 and Escalera de Excelencia CLU-2017-03 to AA and JPB), Agencia Estatal de Investigación (MICIU) (PID2022-138813OB-I00 and FEDER, UE to JPB; RED2022-134407-T to AA), and la Caixa Foundation (grant agreement LCF/PR/HR23/52430016 to JPB), the European Union's Horizon Europe research and innovation program under the MSCA Doctoral Networks 2021 (101072759; FuEl ThEbRaiN In healtThY aging and age-related diseases, ETERNITY, to A.A. and J.P.B.), and the European Research Council (ERC) ... |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | English |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00727/ES/FUNCION ESPECIFICA DE LAS ESPECIES REACTIVAS DE OXIGENO EN LA REPARACION CEREBRAL Y SU IMPACTO EN EL PRONÓSTICO DE ICTUS/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138813OB-I00/ES/IMPACTO DEL METABOLISMO DE LOS ASTROCITOS SOBRE LA REGULACION EPIGENETICA DE LAS FUNCIONES NEURALES DURANTE EL DETERIORO COGNITIVO/; info:eu-repo/grantAgreement/EC/HE/101072759; https://doi.org/10.1016/j.redox.2025.103940; Sí; Redox Biology 88: 103940 (2025); https://hdl.handle.net/10261/416467; http://dx.doi.org/10.13039/501100004587; http://dx.doi.org/10.13039/501100014180; http://dx.doi.org/10.13039/501100011033; http://dx.doi.org/10.13039/501100000780; http://dx.doi.org/10.13039/501100000781; https://api.elsevier.com/content/abstract/scopus_id/105022924786 |
| DOI: | 10.1016/j.redox.2025.103940 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100014180 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100000781 |
| Availability: | https://hdl.handle.net/10261/416467; https://doi.org/10.1016/j.redox.2025.103940; https://doi.org/10.13039/501100004587; https://doi.org/10.13039/501100014180; https://doi.org/10.13039/501100011033; https://doi.org/10.13039/501100000780; https://doi.org/10.13039/501100000781; https://api.elsevier.com/content/abstract/scopus_id/105022924786 |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.9FD5125D |
| Database: | BASE |