Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation

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

doi:10.1016/j.celrep.2021.108952

Cited by 68 publications

(58 citation statements)

References 104 publications

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“…In previous studies, indications of the association between mGluR5 and mitochondrial function have been found. MGluR5 was shown to modulate ATP levels in different types of cells [74][75][76], production of ROS [15,72,75,77], mitochondrial mass [75] and mitochondrial biogenesis [78]. Our study revealed that mGluR5, in addition to these, can also regulate specific mitochondrial proteins, morphology and NADP/H level.…”

Section: Discussionmentioning

confidence: 58%

Reduced mGluR5 Activity Modulates Mitochondrial Function

Gonzalez‐Lozano

Wortel

Loo

et al. 2021

Cells

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The metabotropic glutamate receptor 5 (mGluR5) is an essential modulator of synaptic plasticity, learning and memory; whereas in pathological conditions, it is an acknowledged therapeutic target that has been implicated in multiple brain disorders. Despite robust pre-clinical data, mGluR5 antagonists failed in several clinical trials, highlighting the need for a better understanding of the mechanisms underlying mGluR5 function. In this study, we dissected the molecular synaptic modulation mediated by mGluR5 using genetic and pharmacological mouse models to chronically and acutely reduce mGluR5 activity. We found that next to dysregulation of synaptic proteins, the major regulation in protein expression in both models concerned specific processes in mitochondria, such as oxidative phosphorylation. Second, we observed morphological alterations in shape and area of specifically postsynaptic mitochondria in mGluR5 KO synapses using electron microscopy. Third, computational and biochemical assays suggested an increase of mitochondrial function in neurons, with increased level of NADP/H and oxidative damage in mGluR5 KO. Altogether, our observations provide diverse lines of evidence of the modulation of synaptic mitochondrial function by mGluR5. This connection suggests a role for mGluR5 as a mediator between synaptic activity and mitochondrial function, a finding which might be relevant for the improvement of the clinical potential of mGluR5.

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Section: Discussionmentioning

confidence: 58%

Reduced mGluR5 Activity Modulates Mitochondrial Function

Gonzalez‐Lozano

Wortel

Loo

et al. 2021

Cells

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“…Of note, this temporal relationship indicates other mechanisms may exist. Zehnder et al (2021) discovered that there is a transient high expression of astrocytic mito oxidative metabolism relevant genes, such as mitochondrial biogenesis genes (PGC-1α and PGC-1β), and oxidative phosphorylation genes (Cox5b, Cox41l, Atp5a1, and Cycs) during the third week following birth. Accordingly, astrocytes contain more ATP content and consume more oxygen during the third post-natal week compared to day 50.…”

Section: Astrocyte As a Component Of The Whole Synapsementioning

confidence: 99%

Astrocyte-Neuron Signaling in Synaptogenesis

Shan

Zhang

Fan

et al. 2021

Front. Cell Dev. Biol.

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Astrocytes are the key component of the central nervous system (CNS), serving as pivotal regulators of neuronal synapse formation and maturation through their ability to dynamically and bidirectionally communicate with synapses throughout life. In the past 20 years, numerous astrocyte-derived molecules promoting synaptogenesis have been discovered. However, our understanding of the cell biological basis underlying intra-neuron processes and astrocyte-mediated synaptogenesis is still in its infancy. Here, we provide a comprehensive overview of the various ways astrocytes talk to neurons, and highlight astrocytes’ heterogeneity that allow them to displays regional-specific capabilities in boosting synaptogenesis. Finally, we conclude with promises and future directions on how organoids generated from human induced pluripotent stem cells (hiPSCs) effectively address the signaling pathways astrocytes employ in synaptic development.

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“…The regulation of the mitochondrial network in the processes of astrocytes is associated with the differentiation and maturation of astrocytes, their participation in the maintenance of synapses, and the glial response to damage [70]. The importance of the functioning and morphogenesis of astrocytes was shown for several proteins involved in mitochondrial biogenesis and mitophagy, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a) [71], autophagy-related proteins ATG7 [69] and ATG5 [72], and p62 [73].…”

Section: Mitophagy In Glial Cells In Aging and Neurodegenerationmentioning

confidence: 99%

Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

Сухоруков

Воронков

Баранич

et al. 2021

IJMS

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Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

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Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation

Cited by 68 publications

References 104 publications

Reduced mGluR5 Activity Modulates Mitochondrial Function

Reduced mGluR5 Activity Modulates Mitochondrial Function

Astrocyte-Neuron Signaling in Synaptogenesis

Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

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