ArticleNeuron2021
Oligodendrocytes enhance axonal energy metabolism by deacetylation of mitochondrial proteins through transcellular delivery of SIRT2.
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- The efficacy and potential pharmacological mechanism of Fufang Danshen Tablet in promoting the rehabilitation of ischemic stroke: a meta-analysis andFrontiers in neurologyPooled it
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- Review
- An activity-modulated transport route across myelin (TRAM) for motor-driven organelle transfer in oligodendrocytes.Nature neuroscience · 2026Article
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
- Diabetes and the Metabolic Syndrome as Drivers of Neurodegeneration: Convergent Mechanisms Linking Peripheral Neuropathy and Dementia.Annals of neurology · 2026Review
- Temporal changes in metabolism guide oligodendrocyte precursor cell dynamics in aging and multiple sclerosis.Neuron · 2026Article
- Proteomic comparison of human neural cell-derived extracellular vesicles and parental cells from Alzheimer's disease and cognitively normal individuals.Science China. Life sciences · 2026Article
- Extracellular Vesicles in Stroke: Drivers of Brain-Body Network Crosstalk.Translational stroke research · 2026Review
- Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.International journal of molecular sciences · 2026Review
- Spatiotemporal profiling of white matter lesions and their contribution in the pathologies of Parkinson's disease animal models.GeroScience · 2026Article
- Oligodendrocyte dysfunction contributes to motor deficits and Purkinje cell axonopathy in spinocerebellar ataxia type 1.The Journal of clinical investigation · 2026Article
- Mutant SOD1 expressed by oligodendrocytes aggregates in myelinic nanochannels and accelerates disease progression in familial ALS mice.bioRxiv : the preprint server for biology · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- SNAP-23 mediated vesicular trafficking in oligodendrocytes is necessary to maintain adult myelin integrity in mice.Nature communications · 2026Article
- Metabolic Symbiosis and Vulnerability in the CNS Axon-Myelin Unit.Cellular and molecular neurobiology · 2026Review
- Review
- Neurovascular Unit-Derived Extracellular Vesicles as Regulators of Post-Stroke Pathology and Neurorestoration.Biomolecules · 2026Review
- CREB5 Inhibits Neuronal Ferroptosis via Transactivating ApoL6 to Regulate Lipid Droplet Metabolism After Spinal Cord Injury.CNS neuroscience & therapeutics · 2026Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neurons require mechanisms to maintain ATP homeostasis in axons, which are highly vulnerable to bioenergetic failure. Here, we elucidate a transcellular signaling mechanism by which oligodendrocytes support axonal energy metabolism via transcellular delivery of NAD-dependent deacetylase SIRT2. SIRT2 is undetectable in neurons but enriched in oligodendrocytes and released within exosomes. By deleting sirt2, knocking down SIRT2, or blocking exosome release, we demonstrate that transcellular delivery of SIRT2 is critical for axonal energy enhancement. Mass spectrometry and acetylation analyses indicate that neurons treated with oligodendrocyte-conditioned media from WT, but not sirt2-knockout, mice exhibit strong deacetylation of mitochondrial adenine nucleotide translocases 1 and 2 (ANT1/2). In vivo delivery of SIRT2-filled exosomes into myelinated axons rescues mitochondrial integrity in sirt2-knockout mouse spinal cords. Thus, our study reveals an oligodendrocyte-to-axon delivery of SIRT2, which enhances ATP production by deacetylating mitochondrial proteins, providing a target for boosting axonal bioenergetic metabolism in neurological disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.