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

Fiebig C, Keiner S, Ebert B, Schäffner I, Jagasia R, Lie DC, Beckervordersandforth R (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Frontiers in Molecular Neuroscience Frontiers Research Foundation / Frontiers Media

Book Volume: 12

DOI: 10.3389/fnmol.2019.00040

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.

Authors with CRIS profile

Iris Schäffner Institut für Biochemie Dieter Chichung Lie Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Ruth Beckervordersandforth-Bonk Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Universitätsklinikum Jena DE Germany (DE)

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).

BibTeX: Download