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Updated: Sep 7, 2025

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
CPT2 K79 acetylation regulates platelet life span
Xuemei Fan1, Yang Wang1, Xiaohong Cai2
1Department of Biochemistry and Molecular Cell Biology, and.
Abstract:
The short life span of platelets is a major challenge to platelet transfusion services because of the lack of effective intervention. Here, we found that the accumulation of long-chain acylcarnitines (LCACs) is responsible for mitochondrial damage and platelet storage lesion. Further studies showed that the blockade of fatty acid oxidation and the activation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase/carnitine palmitoyltransferase 1 (CPT1) pathways that promote fatty acid metabolism are important reasons for the accumulation of LCACs. The excessive accumulation of LCACs can cause mitochondrial damage and a short life span of stored platelets. The mechanism study elucidated that NAD+ exhaustion and the subsequent decrease in sirtuin 3 (Sirt3) activity caused an increase in the level of CPT2 K79 acetylation, which is the primary cause of the blockade of fatty acid oxidation and the accumulation of LCACs. Blocking LCAC generation with the inhibitors of AMPK or CPT1, the agonists of Sirt3, and antioxidants tremendously retarded platelet storage lesion in vitro and prolonged the survival of stored platelets in vivo posttransfusion with single or combined use. In summary, we discovered that CPT2 acetylation attenuates fatty acid oxidation and exacerbates platelet storage lesion and may serve as a new target for improving platelet storage quality.
Insights
Platelet storage lesion is caused by long-chain acylcarnitines (LCACs) accumulation, which damages mitochondria. Targeting LCAC generation improves platelet storage and extends posttransfusion survival.
Area of Science:
- Biochemistry
- Hematology
- Cellular Biology
Background:
- Platelet transfusion services face challenges due to the short lifespan of platelets.
- Mitochondrial damage and platelet storage lesion contribute to reduced platelet viability.
Purpose of the Study:
- To investigate the role of long-chain acylcarnitines (LCACs) in platelet storage lesion.
- To identify mechanisms underlying LCAC accumulation and mitochondrial damage in platelets.
- To explore therapeutic strategies for improving platelet storage quality.
Main Methods:
- Investigated the link between fatty acid oxidation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase/carnitine palmitoyltransferase 1 (CPT1) pathways, and LCAC accumulation.
- Elucidated the role of NAD+ exhaustion, sirtuin 3 (Sirt3) activity, and CPT2 acetylation in blocking fatty acid oxidation.
- Tested inhibitors of AMPK or CPT1, Sirt3 agonists, and antioxidants in vitro and in vivo models.
Main Results:
- Accumulation of LCACs was identified as a key factor in mitochondrial damage and platelet storage lesion.
- Blockade of fatty acid oxidation, driven by AMPK/CPT1 pathway activation, leads to LCAC accumulation.
- CPT2 K79 acetylation, resulting from NAD+ depletion and decreased Sirt3 activity, inhibits fatty acid oxidation and promotes LCAC buildup.
- Interventions targeting LCAC generation significantly reduced platelet storage lesion and improved posttransfusion survival.
Conclusions:
- CPT2 acetylation impairs fatty acid oxidation, worsening platelet storage lesion.
- Targeting CPT2 acetylation presents a novel therapeutic strategy for enhancing platelet storage quality and extending platelet lifespan.
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