ArticleNature metabolism2024
Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.Frontiers in immunology · 2026Pooled it
- Human IL-34 Deficiency Primes Microglia Toward Alzheimer's Disease-Associated States.medRxiv : the preprint server for health sciences · 2026Article
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026Review
- Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis.Science (New York, N.Y.) · 2026Article
- Hub genes and diagnostic model associated with mitochondrial function in Alzheimer's disease.Animal models and experimental medicine · 2026Article
- Microglia Mitochondrial Metabolism in Neurological Diseases.Molecular neurobiology · 2026Review
- Time-dependent histological characterization of amyloid-β induced cholinergic and glial alterations and their modulation by dehydroepiandrosterone sulfate (DHEAS).Frontiers in endocrinology · 2026Article
- Dynamic changes in mitochondria support phenotypic flexibility of microglia.Nature communications · 2025Article
- Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment.Nature communications · 2025Article
- Targeting Microglial Connexin43 Hemichannels: A Novel Therapeutic Avenue for Alzheimer's Disease.Neuroscience bulletin · 2025Article
- Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer's disease progression.Science advances · 2025Article
- Hypoxia as a medicine.Science translational medicine · 2025Review
- Complex roles for mitochondrial complexes in microglia.Nature metabolism · 2024Article
- Microglia: roles and genetic risk in Parkinson's disease.Frontiers in neuroscience · 2024Review
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary mitochondrial diseases (PMDs) are associated with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients with PMD show gliosis, and pharmacological depletion of microglia, the innate immune cells of the brain, ameliorates multiple symptoms in a mouse model. Given that microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated with microglia stimulation in vitro (via IL-33 or TAU treatment) was partially changed by complex I (CI) inhibition (via rotenone treatment). In vivo, we generated a mouse model deficient for CI activity in microglia (MGcCI). MGcCI microglia showed metabolic rewiring and gradual transcriptional activation, which led to hypertrophy and dysfunction in juvenile (1-month-old) and adult (3-month-old) stages, respectively. MGcCI mice presented widespread reactive astrocytes, a decrease of synaptic markers accompanied by an increased number of parvalbumin neurons, a behavioral deficit characterized by prolonged periods of immobility, loss of weight and premature death that was partially rescued by pharmacologic depletion of microglia. Our data demonstrate that microglia development depends on mitochondrial CI and suggest a direct microglial contribution to PMDs.
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