Motori, Elisa, Puyal, Julien, Toni, Nicolas ORCID: 0000-0001-5585-268X, Ghanem, Alexander, Angeloni, Cristina, Malaguti, Marco ORCID: 0000-0003-0349-7772, Cantelli-Forti, Giorgio, Berninger, Benedikt ORCID: 0000-0003-2652-2782, Conzelmann, Karl-Klaus ORCID: 0000-0002-8614-3656, Goetz, Magdalena, Winklhofer, Konstanze F., Hrelia, Silvana ORCID: 0000-0001-7857-4512 and Bergami, Matteo ORCID: 0000-0001-5525-5025 (2013). Inflammation-Induced Alteration of Astrocyte Mitochondrial Dynamics Requires Autophagy for Mitochondrial Network Maintenance. Cell Metab., 18 (6). S. 844 - 860. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Motori, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puyal, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toni, NicolasUNSPECIFIEDorcid.org/0000-0001-5585-268XUNSPECIFIED
Ghanem, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angeloni, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malaguti, MarcoUNSPECIFIEDorcid.org/0000-0003-0349-7772UNSPECIFIED
Cantelli-Forti, GiorgioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berninger, BenediktUNSPECIFIEDorcid.org/0000-0003-2652-2782UNSPECIFIED
Conzelmann, Karl-KlausUNSPECIFIEDorcid.org/0000-0002-8614-3656UNSPECIFIED
Goetz, MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winklhofer, Konstanze F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hrelia, SilvanaUNSPECIFIEDorcid.org/0000-0001-7857-4512UNSPECIFIED
Bergami, MatteoUNSPECIFIEDorcid.org/0000-0001-5525-5025UNSPECIFIED
URN: urn:nbn:de:hbz:38-470329
DOI: 10.1016/j.cmet.2013.11.005
Journal or Publication Title: Cell Metab.
Volume: 18
Number: 6
Page Range: S. 844 - 860
Date: 2013
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SPINAL-CORD-INJURY; NITRIC-OXIDE; REACTIVE ASTROCYTES; OXIDATIVE-METABOLISM; FUNCTIONAL RECOVERY; ENERGY-METABOLISM; S-NITROSYLATION; PROTEIN-KINASE; BAX ACTIVATION; FISSIONMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47032

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