Pyruvate dehydrogenase complex E1 subunit α crotonylation modulates cocaine-associated memory through hippocampal neuron activation.
Cell Rep
; 43(8): 114529, 2024 Aug 27.
Article
in En
| MEDLINE
| ID: mdl-39046876
ABSTRACT
Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cocaine
/
Pyruvate Dehydrogenase (Lipoamide)
/
Hippocampus
/
Memory
/
Neurons
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos