ArticleNature metabolism2020
The cross-talk of energy sensing and mitochondrial anchoring sustains synaptic efficacy by maintaining presynaptic metabolism.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Glucose sparing by glycogenolysis (GSG) determines the relationship between brain metabolism and neurotransmission.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Pooled it
- Myelin Dynamics at the Axon-Oligodendrocyte Interface: Adaptive Conduction Homeostasis in Demyelination, Remyelination and White Matter Repair.International journal of molecular sciences · 2026Review
- Mitochondrial molecular diversity in the brain.Current opinion in neurobiology · 2026Review
- Mitochondrial calcium influx-driven bioenergetics selectively enable drug addiction.Nature neuroscience · 2026Article
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
- The therapeutic effect of nicotinamide riboside chloride on ameliorating alcohol-induced neuronal damage with a focus on mitochondrial unfolded protein response and mitophagy.Genes & diseases · 2026Article
- Enhanced axonal mitochondrial motility and neural activity-induced energy deficits destabilize synaptic transmission in models of bipolar disorder.Nature communications · 2026Article
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- Dysregulation of autophagosome-mitochondria contacts contributes to autophagy dysfunction and neurodegeneration in tauopathy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synaptic mitochondria in aging and neurodegenerative diseases: Functional decline and vulnerability.Neural regeneration research · 2026Article
- Physical Exercise Counteracts Impaired Cognition by Improving Mitochondrial Function.International journal of molecular sciences · 2026Review
- Energy stress activates AMPK to arrest mitochondria via phosphorylation of TRAK1.The Journal of cell biology · 2026Article
- Neuronal mitochondrial dynamics: roles in brain disorders and therapeutic potential.Acta pharmacologica Sinica · 2026Article
- A Non-Mitophagy Activity of BNIP3L/NIX in Amygdala Glutamatergic Neurons is Essential for Contextual Fear Memory Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.Alzheimer's research & therapy · 2026Article
- Mitochondrial CaNature metabolism · 2026Article
- Synaptic mitochondrial dysfunction and Alzheimer's disease: from molecular mechanisms to therapeutic strategies.Frontiers in pharmacology · 2026Review
- SIRT3/AMPK-Driven Mitophagy Failure Underlies Methylmercury-Induced Neurotoxicity: Evidence from Humans to Cells.Molecular neurobiology · 2025Article
- Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
Mitochondria supply ATP essential for synaptic transmission. Neurons face exceptional challenges in maintaining energy homoeostasis at synapses. Regulation of mitochondrial trafficking and anchoring is critical for neurons to meet increased energy consumption during sustained synaptic activity. However, mechanisms recruiting and retaining presynaptic mitochondria in sensing synaptic ATP levels remain elusive. Here we reveal an energy signalling axis that controls presynaptic mitochondrial maintenance. Activity-induced presynaptic energy deficits can be rescued by recruiting mitochondria through the AMP-activated protein kinase (AMPK)-p21-activated kinase (PAK) energy signalling pathway. Synaptic activity induces AMPK activation within axonal compartments and AMPK-PAK signalling triggers phosphorylation of myosin VI, which drives mitochondrial recruitment and syntaphilin-mediated anchoring on presynaptic filamentous actin. This pathway maintains presynaptic energy supply and calcium clearance during intensive synaptic activity. Disrupting this signalling cross-talk triggers local energy deficits and intracellular calcium build-up, leading to impaired synaptic efficacy during trains of stimulation and reduced recovery from synaptic depression after prolonged synaptic activity. Our study reveals a mechanistic cross-talk between energy sensing and mitochondria anchoring to maintain presynaptic metabolism, thus fine-tuning short-term synaptic plasticity and prolonged synaptic efficacy.
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Registered trials
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 Socratic graph.