Mitochondrial Dysfunction in Astrocytes Impairs the Generation of Reactive Astrocytes and Enhances Neuronal Cell Death in the Cortex Upon Photothrombotic Lesion

Journal article


Publication Details

Author(s): Fiebig C, Keiner S, Ebert B, Schäffner I, Jagasia R, Lie DC, Beckervordersandforth R
Journal: Frontiers in Molecular Neuroscience
Publication year: 2019
Volume: 12
ISSN: 1662-5099


Abstract

Mitochondria are key organelles in regulating the metabolic state of a cell. In the brain, mitochondrial oxidative metabolism is the prevailing mechanism for neurons to generate ATP. While it is firmly established that neuronal function is highly dependent on mitochondrial metabolism, it is less well-understood how astrocytes function rely on mitochondria. In this study, we investigate if astrocytes require a functional mitochondrial electron transport chain (ETC) and oxidative phosphorylation (oxPhos) under physiological and injury conditions. By immunohistochemistry we show that astrocytes expressed components of the ETC and oxPhos complexes in vivo. Genetic inhibition of mitochondrial transcription by conditional deletion of mitochondrial transcription factor A (Tfam) led to dysfunctional ETC and oxPhos activity, as indicated by aberrant mitochondrial swelling in astrocytes. Mitochondrial dysfunction did not impair survival of astrocytes, but caused a reactive gliosis in the cortex under physiological conditions. Photochemically initiated thrombosis induced ischemic stroke led to formation of hyperfused mitochondrial networks in reactive astrocytes of the perilesional area. Importantly, mitochondrial dysfunction significantly reduced the generation of new astrocytes and increased neuronal cell death in the perilesional area. These results indicate that astrocytes require a functional ETC and oxPhos machinery for proliferation and neuroprotection under injury conditions.


FAU Authors / FAU Editors

Lie, Dieter Chichung Prof. Dr.
Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung
Schäffner, Iris Dr.
Institut für Biochemie


External institutions with authors

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Universitätsklinikum Jena


How to cite

APA:
Fiebig, C., Keiner, S., Ebert, B., Schäffner, I., Jagasia, R., Lie, D.C., & Beckervordersandforth, R. (2019). Mitochondrial Dysfunction in Astrocytes Impairs the Generation of Reactive Astrocytes and Enhances Neuronal Cell Death in the Cortex Upon Photothrombotic Lesion. Frontiers in Molecular Neuroscience, 12. https://dx.doi.org/10.3389/fnmol.2019.00040

MLA:
Fiebig, Christian, et al. "Mitochondrial Dysfunction in Astrocytes Impairs the Generation of Reactive Astrocytes and Enhances Neuronal Cell Death in the Cortex Upon Photothrombotic Lesion." Frontiers in Molecular Neuroscience 12 (2019).

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Last updated on 2019-08-03 at 09:08