Acetyl-CoA availability regulates neuronal metabolism, growth, and synaptic activity
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Le résumé fourni par la source
The metabolite acetyl-CoA plays a central role in cellular metabolic homeostasis. As part of the secretory pathway, acetyl-CoA is imported into the endoplasmic reticulum (ER) by a membrane-bound transporter AT-1 (SLC33A1). AT-1 has been linked to peripheral neuropathy (heterozygous mutations), developmental delay with premature death (homozygous mutations) and intellectual disability with progeria (duplication). These phenotypes can be reproduced in the mouse. Here, we show that AT-1 overexpression in primary neurons impacts diverse phenotypes related to neuronal function and plasticity. At the gene level, AT-1 induces brain aging signatures, and key differences in ribosomal and synaptic processes were identified in both the transcriptome and the proteome. Changes in mitochondria-associated pathways were reflected in an increase in expression of mitochondrial master regulator PGC-1α and its target genes. Functionally, marked differences in mitochondrial membrane potential, architecture, and respiration were detected. Tracing experiments indicated altered glucose utilization in glycogen storage and nucleotide production. Shifts in redox metabolism were linked to differences in levels of NAD-dependent SIRT1 and CtBP2, with consequences for acetylated lysine modification. Depletion of lipid stores was associated with greater plasticity in fuel substrate utilization and a major shift in cellular lipid composition. These broad-scale changes in metabolism were coincident with reduced expression of synaptic proteins and reduced activity among synaptic networks, indicating that neuronal electrophysiology and network communication are coordinated at least in part through neuronal acetyl-CoA metabolism.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Acetyl-CoA availability regulates neuronal metabolism, growth, and synaptic activity
- Date Crossref
- 20/01/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Wisconsin–Madison pays non établi dans la noticeUniversité ou école supérieure
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Morgridge Institute for Research pays non établi dans la noticeOrganisation à but non lucratif
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Howard Hughes Medical Institute pays non établi dans la noticeStructure de recherche
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Geriatric Research Education and Clinical Center pays non établi dans la noticeÉtablissement de santé
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William S. Middleton Memorial Veterans Hospital pays non établi dans la noticeÉtablissement de santé
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University of Wisconsin-Madison Department of Medical Microbiology and Immunology pays non établi dans la noticeUniversité ou école supérieure
University of Wisconsin–Madison, Morgridge Institute for Research et Howard Hughes Medical Institute, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.