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Open Access Green as soon as Postprint is submitted to ZB.
Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance.
Cell Metab. 18, 844-859 (2013)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Spinal-cord-injury ; Nitric-oxide ; Reactive Astrocytes ; Oxidative-metabolism ; Functional Recovery ; Energy-metabolism ; S-nitrosylation ; Protein-kinase ; Bax Activation ; Fission
ISSN (print) / ISBN
1550-4131
e-ISSN
1932-7420
Journal
Cell Metabolism
Quellenangaben
Volume: 18,
Issue: 6,
Pages: 844-859
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)