Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant “autophagy checkpoint”

Léa Montégut, Mahmoud Abdellatif, Omar Motiño, Frank Madeo, Isabelle Martins, Victor Quesada, Carlos López-Otín, Guido Kroemer

    Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

    16 Citations (Scopus)

    Résumé

    Acyl coenzyme A binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a phylogenetically ancient protein present in some eubacteria and the entire eukaryotic radiation. In several eukaryotic phyla, ACBP/DBI transcends its intracellular function in fatty acid metabolism because it can be released into the extracellular space. This ACBP/DBI secretion usually occurs in response to nutrient scarcity through an autophagy-dependent pathway. ACBP/DBI and its peptide fragments then act on a range of distinct receptors that diverge among phyla, namely metabotropic G protein-coupled receptor in yeast (and likely in the mammalian central nervous system), a histidine receptor kinase in slime molds, and ionotropic gamma-aminobutyric acid (GABA)A receptors in mammals. Genetic or antibody-mediated inhibition of ACBP/DBI orthologs interferes with nutrient stress-induced adaptations such as sporulation or increased food intake in multiple species, as it enhances lifespan or healthspan in yeast, plant leaves, nematodes, and multiple mouse models. These lifespan and healthspan-extending effects of ACBP/DBI suppression are coupled to the induction of autophagy. Altogether, it appears that neutralization of extracellular ACBP/DBI results in “autophagy checkpoint inhibition” to unleash the anti-aging potential of autophagy. Of note, in humans, ACBP/DBI levels increase in various tissues, as well as in the plasma, in the context of aging, obesity, uncontrolled infection or cardiovascular, inflammatory, neurodegenerative, and malignant diseases.

    langue originaleAnglais
    Numéro d'articlee13910
    journalAging Cell
    Volume22
    Numéro de publication9
    Les DOIs
    étatPublié - 1 sept. 2023

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