TY  - JOUR
AU  - Motori, Elisa
AU  - Puyal, Julien
AU  - Toni, Nicolas
AU  - Ghanem, Alexander
AU  - Angeloni, Cristina
AU  - Malaguti, Marco
AU  - Cantelli-Forti, Giorgio
AU  - Berninger, Benedikt
AU  - Conzelmann, Karl-Klaus
AU  - Götz, Magdalena
AU  - Winklhofer, Konstanze F
AU  - Hrelia, Silvana
AU  - Bergami, Matteo
TI  - Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance.
JO  - Cell metabolism
VL  - 18
IS  - 6
SN  - 1550-4131
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DZNE-2020-03478
SP  - 844-859
PY  - 2013
AB  - 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.
KW  - Animals
KW  - Astrocytes: cytology
KW  - Astrocytes: drug effects
KW  - Astrocytes: metabolism
KW  - Autophagy
KW  - Autophagy-Related Protein 7
KW  - Cells, Cultured
KW  - Cytokines: metabolism
KW  - Dynamins: metabolism
KW  - Inflammation: metabolism
KW  - Inflammation: pathology
KW  - Interferon-gamma: pharmacology
KW  - Interleukin-1beta: metabolism
KW  - Lipopolysaccharides: toxicity
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Microtubule-Associated Proteins: genetics
KW  - Microtubule-Associated Proteins: metabolism
KW  - Mitochondria: drug effects
KW  - Mitochondria: metabolism
KW  - Mitochondrial Dynamics: drug effects
KW  - Nitric Oxide Synthase Type II: metabolism
KW  - Phosphorylation
KW  - Reactive Oxygen Species: metabolism
KW  - Atg7 protein, mouse (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - Interleukin-1beta (NLM Chemicals)
KW  - Lipopolysaccharides (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Interferon-gamma (NLM Chemicals)
KW  - Nitric Oxide Synthase Type II (NLM Chemicals)
KW  - Dnm1l protein, mouse (NLM Chemicals)
KW  - Dynamins (NLM Chemicals)
KW  - Autophagy-Related Protein 7 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24315370
DO  - DOI:10.1016/j.cmet.2013.11.005
UR  - https://pub.dzne.de/record/137156
ER  -