Acyl coenzyme A binding protein (<scp>ACBP</scp>): An aging‐ and disease‐relevant “autophagy checkpoint”

Montégut, Léa; Abdellatif, Mahmoud; Motiño, Omar; Madeo, Frank; Martins, Isabelle; Quesada, Vı́ctor; López-Otı́n, Carlos; Kroemer, Guido

doi:10.1111/acel.13910

Cited by 13 publications

(2 citation statements)

References 145 publications

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“…This also applies to other organs. Thus, the ACBP/DBI neutralization protects against lung fibrosis induced by bleomycin, as well as against myocardium infarction [ 9 ] and anthracycline-induced cardiac aging [ 24 , 25 ]. Moreover, ACBP/DBI knockout protects against stroke in a mouse model [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide

Anagnostopoulos,

Saavedra,

Lambertucci

et al. 2024

Cell Death Dis

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Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.

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Section: Discussionmentioning

confidence: 99%

Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide

Anagnostopoulos,

Saavedra,

Lambertucci

et al. 2024

Cell Death Dis

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“…Some of the senescent cells evolve a senescence-associated secretory phenotype (SASP) that recruits the immune system to clear dysfunctional senescent cells since they are resistant to apoptosis [ 3 ]. An increase in age leads to an increase in the senescent cell population and dysfunctional autophagy rate in different metabolic settings [ 4 , 5 , 6 ]. Their participation in different settings of aging has led to both being considered hallmarks of aging [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Interaction between Autophagy and Senescence in Pancreatic Beta Cells

Hela,

Aguayo-Mazzucato

2023

Biology

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Aging leads to an increase in cellular stress due to the fragility of the organism and the inability to cope with it. In this setting, there is a higher chance of developing different cardiometabolic diseases like diabetes. Cellular senescence and autophagy, both hallmarks of aging and stress-coping mechanisms, have gained increased attention for their role in the pathophysiology of diabetes. Studies show that impairing senescence dampens and even prevents diabetes while the role of autophagy is more contradictory, implying a context- and disease-stage-dependent effect. Reports show conflicting data about the effect of autophagy on senescence while the knowledge about this interaction in beta cells remains scarce. Elucidating this interaction between autophagy and senescence in pancreatic beta cells will lead to an identification of their respective roles and the extent of the effect each mechanism has on beta cells and open new horizons for developing novel therapeutic agents. To help illuminate this relationship we will review the latest findings of cellular senescence and autophagy with a special emphasis on pancreatic beta cells and diabetes.

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Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets

Ghatak,

Diedrich,

Talantova

et al. 2024

Advanced Science

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Standard single‐cell (sc) proteomics of disease states inferred from multicellular organs or organoids cannot currently be related to single‐cell physiology. Here, a scPatch‐Clamp/Proteomics platform is developed on single neurons generated from hiPSCs bearing an Alzheimer's disease (AD) genetic mutation and compares them to isogenic wild‐type controls. This approach provides both current and voltage electrophysiological data plus detailed proteomics information on single‐cells. With this new method, the authors are able to observe hyperelectrical activity in the AD hiPSC‐neurons, similar to that observed in the human AD brain, and correlate it to ≈1400 proteins detected at the single neuron level. Using linear regression and mediation analyses to explore the relationship between the abundance of individual proteins and the neuron's mutational and electrophysiological status, this approach yields new information on therapeutic targets in excitatory neurons not attainable by traditional methods. This combined patch‐proteomics technique creates a new proteogenetic‐therapeutic strategy to correlate genotypic alterations to physiology with protein expression in single‐cells.

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

Cited by 13 publications

References 145 publications

Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide

Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide

Interaction between Autophagy and Senescence in Pancreatic Beta Cells

Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets

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