ArticleDevelopmental cell2021
Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation.
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
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- Targeting the powerhouse: the mitochondrial perspective on gentamicin-induced kidney injury.Archives of toxicology · 2026Review
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- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Mitochondrial CaNature metabolism · 2026Article
- Neuronal differentiation regulator CEND1 coordinately suppresses tumor growth and energetics via AMPK signaling in brain glioma.Cell & bioscience · 2025Article
- AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth.Developmental cell · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Increased Complement C4 in a Sparse Neuronal Subset Induces Network-Wide Transcriptomic Alterations in the Prefrontal Cortex.bioRxiv : the preprint server for biology · 2025Article
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- Pioglitazone Alleviates β1-adrenergic Receptor Antibody-induced Atrial Fibrillation SusceptivityCurrent medicinal chemistry · 2025Article
- Roles of small GTPases in cardiac hypertrophy (Review).Molecular medicine reports · 2024Review
- The Long Non-Coding RNA NR3C2-8:1 Promotes p53-Mediated Apoptosis through the miR-129-5p/USP10 Axis in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2024Article
- Osteoclasts control endochondral ossification via regulating acetyl-CoA availability.Bone research · 2024Article
- Activation of GPER1 by G1 prevents PTSD-like behaviors in mice: Illustrating the mechanisms from BDNF/TrkB to mitochondria and synaptic connection.CNS neuroscience & therapeutics · 2024Article
- Rheb1 is required for limb growth through regulating chondrogenesis in growth plate.Cell and tissue research · 2024Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Recent progress of methods for cuproptosis detection.Frontiers in molecular biosciences · 2024Review
- Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury.Neural regeneration research · 2023Article
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
Neuronal activity increases energy consumption and requires balanced production to maintain neuronal function. How activity is coupled to energy production remains incompletely understood. Here, we report that Rheb regulates mitochondrial tricarboxylic acid cycle flux of acetyl-CoA by activating pyruvate dehydrogenase (PDH) to increase ATP production. Rheb is induced by synaptic activity and lactate and dynamically trafficked to the mitochondrial matrix through its interaction with Tom20. Mitochondria-localized Rheb protein is required for activity-induced PDH activation and ATP production. Cell-type-specific gain- and loss-of-function genetic models for Rheb reveal reciprocal changes in PDH phosphorylation/activity, acetyl-CoA, and ATP that are not evident with genetic or pharmacological manipulations of mTORC1. Mechanistically, Rheb physically associates with PDH phosphatase (PDP), enhancing its activity and association with the catalytic E1α-subunit of PDH to reduce PDH phosphorylation and increase its activity. Findings identify Rheb as a nodal point that balances neuronal activity and neuroenergetics via Rheb-PDH axis.
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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.