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Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation

Zehnder, Tamara ; Petrelli, Francesco ; Romanos, Jennifer ; De Oliveira Figueiredo, Eva C. ; Lewis, Tommy L. ; Déglon, Nicole ; Polleux, Franck ; Santello, Mirko ; Bezzi, Paola

Cell reports (Cambridge), 2021-04, Vol.35 (2), p.108952, Article 108952 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation
Autor: Zehnder, Tamara ; Petrelli, Francesco ; Romanos, Jennifer ; De Oliveira Figueiredo, Eva C. ; Lewis, Tommy L. ; Déglon, Nicole ; Polleux, Franck ; Santello, Mirko ; Bezzi, Paola
Assuntos: Animals ; Animals, Newborn ; astrocyte ; Astrocytes - cytology ; Astrocytes - metabolism ; Brain - cytology ; Brain - growth & development ; Brain - metabolism ; Cell Differentiation ; Cell Proliferation ; Electron Transport Complex IV - genetics ; Electron Transport Complex IV - metabolism ; Gene Expression Regulation, Developmental ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Humans ; Male ; mGluR5 ; Mice ; Mice, Transgenic ; mitochondria ; Mitochondria - genetics ; Mitochondria - metabolism ; Mitochondria - ultrastructure ; Mitochondrial Proton-Translocating ATPases - genetics ; Mitochondrial Proton-Translocating ATPases - metabolism ; Neurogenesis - genetics ; Organelle Biogenesis ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism ; PGC-1α ; Primary Cell Culture ; Receptor, Metabotropic Glutamate 5 - genetics ; Receptor, Metabotropic Glutamate 5 - metabolism ; Synapses - genetics ; Synapses - metabolism ; Synapses - ultrastructure ; Synaptic Transmission - genetics
É parte de: Cell reports (Cambridge), 2021-04, Vol.35 (2), p.108952, Article 108952
Descrição: The mechanisms controlling the post-natal maturation of astrocytes play a crucial role in ensuring correct synaptogenesis. We show that mitochondrial biogenesis in developing astrocytes is necessary for coordinating post-natal astrocyte maturation and synaptogenesis. The astrocytic mitochondrial biogenesis depends on the transient upregulation of metabolic regulator peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), which is controlled by metabotropic glutamate receptor 5 (mGluR5). At tissue level, the loss or downregulation of astrocytic PGC-1α sustains astrocyte proliferation, dampens astrocyte morphogenesis, and impairs the formation and function of neighboring synapses, whereas its genetic re-expression is sufficient to restore the mitochondria compartment and correct astroglial and synaptic defects. Our findings show that the developmental enhancement of mitochondrial biogenesis in astrocytes is a critical mechanism controlling astrocyte maturation and supporting synaptogenesis, thus suggesting that astrocytic mitochondria may be a therapeutic target in the case of neurodevelopmental and psychiatric disorders characterized by impaired synaptogenesis. [Display omitted] •Developing astrocytes contain a highly interconnected functional network of mitochondria•Mitochondrial biogenesis in developing astrocytes is controlled by PGC-1α•mGluR5 signaling modulates PGC-1α levels in developing astrocytes•Deletion of PGC1-1α and mGluR5 impairs astrocyte maturation and synaptogenesis Zehnder et al. demonstrate that proper levels of PGC-1α are necessary to induce a correct mitochondrial biogenesis in developing astrocytes and, consequently, to coordinate post-natal astrocyte morphogenesis and synaptogenesis.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation

Zehnder, Tamara ; Petrelli, Francesco ; Romanos, Jennifer ; De Oliveira Figueiredo, Eva C. ; Lewis, Tommy L. ; Déglon, Nicole ; Polleux, Franck ; Santello, Mirko ; Bezzi, Paola

United States: Elsevier Inc

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