Inflammation-Induced Alteration of Astrocyte Mitochondrial Dynamics Requires Autophagy for Mitochondrial Network Maintenance
Open accessAbstract
Accumulating evidence suggests that changes in the metabolic signature of astrocytes underlie their response to neuroinflammation, but how proinflammatory stimuli induce these changes is poorly understood. By monitoring astrocytes following acute cortical injury, we identified a differential and region-specific remodeling of their mitochondrial network: while astrocytes within the penumbra of the lesion undergo mitochondrial elongation, those located in the core-the area invaded by proinflammatory cells-experience transient mitochondrial fragmentation. In brain slices, proinflammatory stimuli reproduced localized changes in mitochondrial dynamics, favoring fission over fusion. This effect was triggered by Drp1 phosphorylation and ultimately resulted in reduced respiratory capacity. Furthermore, maintenance of the mitochondrial architecture critically depended on the induction of autophagy. Deletion of Atg7, required for autophagosome formation, prevented the reestablishment of tubular mitochondria, leading to marked reactive oxygen species accumulation and cell death. Thus, our data reveal autophagy to be essential for regenerating astrocyte mitochondrial networks during inflammation.
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Fragmented mitochondria are often associated with decreased ATP production and compromised membrane potential, ultimately contributing to cellular dysfunction and pathological conditions.
“Fragmented mitochondria are often associated with decreased ATP production and compromised membrane potential, ultimately contributing to cellular dysfunction and pathological conditions (Motori et al., 2013; Joshi et al., 2019; Batista et al., 2021).”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Motori et al., 2013
In reactive gliosis, intact mitochondrial health is essential and is maintained through autophagy, such that astrocyte-specific deletion of Atg7 perturbs the balance of mitochondrial dynamics to favor fission over fusion and thereby reduces oxidative capacity.
“In reactive gliosis, a process unique to astrocytes, intact mitochondrial health is essential and is maintained through autophagy, such that astrocyte-specific deletion of Atg7 perturbs the balance of mitochondrial dynamics to favor fission over fusion and thereby reduces oxidative capacity [401].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [401]
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“to favor fission over fusion and thereby reduces oxidative capacity [401].”
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Aging promotes an increase in mitochondrial fragmentation in astrocytes
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- Authors
- Motori, E., Puyal, J., Toni, N., Ghanem, A., Angeloni, C., Malaguti, M., Cantelli-Forti, G., Berninger, B., Conzelmann, K.-K., Götz, M., Winklhofer, K. F., Hrelia, S., & Bergami, M.
- Affiliations
- Adolf-Butenandt-Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie (DE)
- University of Lausanne (CH)
- Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie (DE)
- University of Bologna (IT)
- Johannes Gutenberg University Mainz (DE)
- Helmholtz Munich (DE)
- German Center for Neurodegenerative Diseases (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Corresponding author
- Motori, Elisa
- Bergami, Matteo
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 18
- Issue
- 6
- Pages
- 844-859
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1983832155
- Cited by
- 249
- References
- 57
- Citations by year
- 2026: 11 · 2025: 28 · 2024: 19 · 2023: 20 · 2022: 9 · 2021: 31 · 2020: 34 · 2019: 17 · 2018: 22 · 2017: 17 · 2016: 13 · 2015: 19 · 2014: 9
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- IRIS (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion, cc-by)
- DZNE Pub (submittedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- astrocytes, neuroinflammation, mitochondrial dynamics, mitochondrial fission, mitochondrial fusion, Drp1 phosphorylation, autophagy, ATG7, mitochondrial network remodeling, cortical injury, penumbra, reactive oxygen species, astrocyte cell death, mitochondrial respiratory capacity
- MeSH terms
- Autophagy-Related Protein 7, Animals, Astrocytes, Autophagy, Cells, Cultured, Inflammation, Interferon-gamma, Lipopolysaccharides, Male, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Mitochondria, Phosphorylation, Cytokines, Reactive Oxygen Species, Dynamins, Mice, Nitric Oxide Synthase Type II, Interleukin-1beta, Mitochondrial Dynamics
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