Permeability Transition Pore-Mediated Mitochondrial Superoxide Flashes Regulate Cortical Neural Progenitor Differentiation
Open accessAbstract
In the process of neurogenesis, neural progenitor cells (NPCs) cease dividing and differentiate into postmitotic neurons that grow dendrites and an axon, become excitable, and establish synapses with other neurons. Mitochondrial biogenesis and aerobic metabolism provide energy substrates required to support the differentiation, growth and synaptic activity of neurons. Mitochondria may also serve signaling functions and, in this regard, it was recently reported that mitochondria can generate rapid bursts of superoxide (superoxide flashes), the frequency of which changes in response to environmental conditions and signals including oxygen levels and Ca(2+) fluxes. Here we show that the frequency of mitochondrial superoxide flashes increases as embryonic cerebral cortical neurons differentiate from NPCs, and provide evidence that the superoxide flashes serve a signaling function that is critical for the differentiation process. The superoxide flashes are mediated by mitochondrial permeability transition pore (mPTP) opening, and pharmacological inhibition of the mPTP suppresses neuronal differentiation. Moreover, superoxide flashes and neuronal differentiation are inhibited by scavenging of mitochondrial superoxide. Conversely, manipulations that increase superoxide flash frequency accelerate neuronal differentiation. Our findings reveal a regulatory role for mitochondrial superoxide flashes, mediated by mPTP opening, in neuronal differentiation.
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Partial, short duration openings of mPTP can generate a pulse of H2O2, Ca2+ and superoxide that may serve as signals for several physiological processes.
“Partial, short duration openings of mPTP can generate a pulse of H2O2, Ca2+ and superoxide that may serve as signals for several physiological processes [11,12,13,69,70].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [12]
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- Authors
- Hou, Y., Mattson, M. P., & Cheng, A.
- Affiliations
- National Institute on Aging (US)
- Johns Hopkins University (US)
- Corresponding author
- Mattson, Mark P.
- Cheng, Aiwu
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-10-08
- Volume
- 8
- Issue
- 10
- Pages
- e76721
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3792897
- OpenAlex
- W2010101510
- Cited by
- 39
- References
- 36
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 3 · 2020: 6 · 2019: 1 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 10
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute on Aging
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- mitochondrial permeability transition pore, neuronal differentiation, neural progenitor cells, cerebral cortex, neurogenesis, mitochondrial signaling, superoxide radical scavenging, mitochondrial biogenesis, aerobic metabolism
- MeSH terms
- Mitochondrial Permeability Transition Pore, Animals, Atractyloside, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Glial Fibrillary Acidic Protein, Immunohistochemistry, Mice, Inbred C57BL, Mitochondria, Superoxides, Superoxide Dismutase, Time Factors, Tubulin, Immunoblotting, Cyclosporine, Microscopy, Confocal, Mitochondrial Proteins, Mitochondrial Membrane Transport Proteins, Cytochromes c, Mice, Membrane Potential, Mitochondrial, SOXB1 Transcription Factors, Neural Stem Cells
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