IRAP Drives Ribosomal Degradation to Refuel Energy for Platelet Activation during Septic Thrombosis
Source abstract
Abstract
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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Platelet Disorders and Treatments · Complement system in diseases · Streptococcal Infections and Treatments
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
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 400038 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 400037 China
Medical Center of Hematology Xinqiao Hospital State Key Laboratory of Trauma and Chemical Poisoning Army Medical University (Third Military Medical University) Chongqing 400037 China
Funding
National Natural Science Foundation of China
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