Regulation of autophagy by cytosolic acetyl-coenzyme A.
Level 5 - mechanism / opinion, no new human data
Preclinical bench and animal research without human clinical data
PubMed 24560926 · doi:10.1016/j.molcel.2014.01.016
What was done
Researchers investigated the role of cytosolic acetyl-coenzyme A (AcCoA) in metabolic signaling and autophagy regulation using cultured human cells and mouse models, including a cardiac pressure overload model. They manipulated cytosolic AcCoA levels to assess impacts on cytoplasmic protein acetylation, EP300 acetyltransferase activity, and autophagy induction.
What was found
The abstract reports no numerical values or effect sizes. Directionally, nutrient starvation depleted AcCoA, decreased cytoplasmic protein acetylation, and triggered autophagy. Increasing cytosolic AcCoA suppressed autophagy, while reducing AcCoA induced autophagy in both human cell cultures and mice. Sustaining high AcCoA inhibited autophagy in a mouse model of cardiac pressure overload. Mechanistically, AcCoA depletion decreased EP300 activity, and EP300 was required for high AcCoA levels to suppress autophagy.
Why it matters
This study identifies cytosolic AcCoA as a central metabolic sensor linking nutritional status to autophagy through EP300-mediated protein acetylation, highlighting potential metabolic pathways for therapeutic modulation of autophagy.
Limits
Findings are limited to preclinical in vitro cell culture and rodent models, so direct relevance to human physiology and disease remains unverified. The abstract does not provide sample sizes, effect sizes, or statistical metrics.
Cited by
- supports Depleting glucose, amino acids, or fatty acids lowers cytosolic acetyl-CoA levels, which causes cytosolic protein deacetylation and stimulates autophagy.
- supports ATP citrate lyase is the primary enzyme generating the cytosolic acetyl-CoA pool, and hydroxycitrate inhibits it, causing acetyl-CoA depletion, deacetylation, and autophagy.