Chemoproteomic Profiling of Signaling Metabolite Fructose-1,6-Bisphosphate Interacting Proteins in Living Cells.
J Am Chem Soc
; 146(22): 15155-15166, 2024 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-38775806
ABSTRACT
Fructose-1,6-bisphosphate (FBP), a cellular endogenous sugar metabolite in the glycolytic pathway, has recently been reported to act as a signaling molecule to regulate various cellular events through the engagement of important proteins. Though tremendous progress has been made in identifying specific FBP-protein interactions, the comprehensive identification of FBP-interacting proteins and their regulatory mechanisms remains largely unexplored. Here, we describe a concise synthetic approach for the scalable preparation of a photoaffinity FBP probe that enables the quantitative chemoproteomic profiling of FBP-protein interactions based on photoaffinity labeling (PAL) directly in living cells. Using such a protocol, we captured known FBP targets including PKM2 and MDH2. Furthermore, among unknown FBP-interacting proteins, we identified a mitochondrial metabolic enzyme aldehyde dehydrogenase 2 (ALDH2), against which FBP showed inhibitory activity and resulted in cellular ROS upregulation accompanied by mitochondrial fragmentation. Our findings disclosed a new mode of glucose signaling mediating by the FBP-ALDH2-ROS axis.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteómica
/
Aldehído Deshidrogenasa Mitocondrial
/
Fructosadifosfatos
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2024
Tipo del documento:
Article
País de afiliación:
China