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Mitochondrial complex I activity in microglia sustains neuroinflammation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE248175 | GEO | 2024/01/10

REPOSITORIES: GEO

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Mitochondrial complex I activity in microglia sustains neuroinflammation.

Project description:Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

| S-EPMC10990929 | biostudies-literature

Mitochondrial complex I activity in microglia sustains neuroinflammation [bulk]

Project description:Sustained smouldering, or low grade, activation of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis (MS). Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells. However, how these metabolic features act to perpetuate neuroinflammation is currently unknown. Using a multiomics approach, we identified a new molecular signature that perpetuates the activation of myeloid cells through mitochondrial complex I (CI) activity driving reverse electron transport (RET) and the production of reactive oxygen species (ROS). Blocking CI activity in pro-inflammatory microglia protected the central nervous system (CNS) against neurotoxic damage and improved functional outcomes in animal disease models in vivo. Our data show that mitochondrial CI in microglia is a potential new therapeutic target to foster neuroprotection in smouldering inflammatory CNS disorders.

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Mitochondrial complex I activity in microglia sustains neuroinflammation [scRNA-seq]

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Mitochondrial complex I activity in microglia sustains neuroinflammation [scRNA-seq II]

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Mitochondrial complex I activity in microglia sustains neuroinflammation [scRNA-seq III]

2024-01-10 | GSE248174 | GEO