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© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Platelets play crucial roles in multiple pathophysiological processes after energy‐dependent activation. It is puzzling how such a small cellular debris has abundant energy supply. In this study, it is shown that insulin‐regulated aminopeptidase (IRAP), a type II transmembrane protein, is a key regulator for platelet activation by promoting energy regeneration during septic thrombosis. Through interaction with certain endosome membrane proteins, IRAP can not only promote granule release, but also facilitate lysosomal degradation of theoretically discarded ribosomes in an mTORC1‐ and S‐acylation‐dependent manner in activated platelets. Plentiful amino acids obtained from IRAP‐mediated ribophagy are recruited to aerobic glycolysis and then promote energy metabolism reprogramming, thereby producing abundant energy for platelet life extension and prolonged activation. Consequently, targeted blocking IRAP can dramatically alleviate platelet hyperactivation and septic thrombosis.

Details

Title
IRAP Drives Ribosomal Degradation to Refuel Energy for Platelet Activation during Septic Thrombosis
Author
Xu, Baichuan 1   VIAFID ORCID Logo  ; Ye, Xianpeng 1 ; Sun, Kangfu 1 ; Chen, Liang 1 ; Wen, Zhaoyang 1 ; Lan, Qigang 2 ; Chen, Jun 1 ; Chen, Mo 1 ; Shen, Mingqiang 1 ; Wang, Song 1 ; Xu, Yang 1 ; Zhang, Xi 3 ; Zhao, Jinghong 2 ; Wang, Junping 1 ; Chen, Shilei 1   VIAFID ORCID Logo 

 State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China 
 Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China 
 Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing, China 
Section
Research Article
Publication year
2025
Publication date
Apr 1, 2025
Publisher
John Wiley & Sons, Inc.
e-ISSN
21983844
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3185984267
Copyright
© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.