Spermidine induces autophagy by inhibiting the acetyltransferase EP300.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture and biochemical mechanistic study without human participants.
PubMed 25526088 · doi:10.1038/cdd.2014.215
What was done
Researchers evaluated the effects of natural dietary compounds (spermidine, anacardic acid, curcumin, and garcinol) on total cellular acetylation, autophagic flux markers (GFP-LC3 puncta formation and p62/SQSTM1 depletion), and mTORC1 activity in cultured human cells. They conducted a knockdown screen of 43 candidate acetyltransferases to identify enzymes whose loss activates autophagy while inhibiting mTORC1. They also assessed the pharmacological EP300 inhibitor C646 in nucleated cells and enucleated cytoplasts, and tested the direct inhibition of recombinant EP300 enzymatic activity by candidate compounds in vitro.
What was found
No quantitative values, concentrations, or effect sizes are reported in the abstract. Spermidine, anacardic acid, curcumin, and garcinol reduced cellular acetylation, promoted markers of autophagic flux, and inhibited mTORC1. Knockdown of EP300 and NAA20 (NAT5) specifically triggered autophagy and inhibited mTORC1 among the 43 tested acetyltransferases. Pharmacological inhibition with C646 stimulated autophagy in both nucleated cells and cytoplasts. Spermidine, anacardic acid, curcumin, and garcinol all directly inhibited recombinant EP300 acetyltransferase activity in vitro.
Why it matters
This study defines EP300 as an endogenous repressor of autophagy and establishes that spermidine and similar natural compounds promote autophagy and suppress mTORC1 by directly inhibiting EP300.
Limits
The abstract provides no numerical data, baseline measures, or statistical effect estimates. All experiments were performed in cultured cells, cytoplasts, and cell-free enzyme assays; systemic pharmacokinetics, physiological dosing, and effects in intact living organisms or humans were not tested.
Cited by
- supports Spermidine and C646 induce autophagy and protein deacetylation by specifically inhibiting the protein acetyltransferase EP300.