ArticleProceedings of the National Academy of Sciences of the United States of America2016
Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers.
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Who cites it
251 citing papers in PubMed, 490 citations in OpenAlex.
- Mitotic assembly of respiratory supercomplexes ensures accurate cell division and fuels tumor growth.EMBO reports · 2026Article
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- Astrocytic PI3Kα controls synaptic plasticity and cognitive function via serine metabolism.Nature communications · 2026Article
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
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- Mitochondria-ER contacts function as an iron supply hub.Nature cell biology · 2026Article
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- A multi-organ spatial metabolomic atlas of exercising mice reveals neuronal Complex I as a convergent and sufficient axis for tau pathology reduction in PS19.bioRxiv : the preprint server for biology · 2026Article
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- Tuning the Fire: Context-Dependent Mitochondrial ROS Signaling, Mitohormesis, and Redox-Modulating Interventions.Biomolecules · 2026Review
- Hyperacetylation escalates myocardial susceptibility to ischemia reperfusion injury by mediating mitochondrial supercomplexes assembly in T2DM.Redox biology · 2026Article
- Cuproptosis-Related Genes in Immune Infiltration and Diagnosis in Hepatitis B Virus-Related Acute Liver Failure.Exploration (Beijing, China) · 2026Article
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage.bioRxiv : the preprint server for biology · 2026Article
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- Mitochondrial CaNature metabolism · 2026Article
- Signaling roles for astrocytic lipid metabolism in brain function.EMBO reports · 2026Review
- Intestinal metabolite TMAO promotes CKD progression by stimulating macrophage M2 polarization through histone H4 lysine 12 lactylation.Cell death and differentiation · 2026Article
- Review
- Mitochondrial CaBiomolecules · 2026Review
191 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences and the structural organization of the mitochondrial respiratory chain is unknown. Here, we investigated this issue and found that, in neurons, mitochondrial complex I is predominantly assembled into supercomplexes, whereas in astrocytes the abundance of free complex I is higher. The presence of free complex I in astrocytes correlates with the severalfold higher reactive oxygen species (ROS) production by astrocytes compared with neurons. Using a complexomics approach, we found that the complex I subunit NDUFS1 was more abundant in neurons than in astrocytes. Interestingly, NDUFS1 knockdown in neurons decreased the association of complex I into supercomplexes, leading to impaired oxygen consumption and increased mitochondrial ROS. Conversely, overexpression of NDUFS1 in astrocytes promoted complex I incorporation into supercomplexes, decreasing ROS. Thus, complex I assembly into supercomplexes regulates ROS production and may contribute to the bioenergetic differences between neurons and astrocytes.
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Registered trials
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