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Updated: Dec 12, 2025

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Siderophores induce mitophagy-dependent apoptosis in platelets
Wenyuan Wang1, Yufeng Lu1, Yulin Wang2
1Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Background:
Siderophores are major virulent factors of K. pneumoniae, and their roles are iron chelators in the host. Several studies have shown that iron chelation could result in mitochondrial dysfunction and increase the production of reactive oxygen species (ROS), which further induces cell mitophagy and apoptosis. However, the impacts of siderophores on platelets are still unknown.
Methods:
We obtained platelets of healthy volunteers to perform in vitro experiments in our study and treated platelets with different siderophores. Mitophagy related proteins (TOMM20, TIMM23, LC3, and p62), signal proteins (PINK1/Parkin and BNIP3), and apoptosis protein (caspase3) in platelets were analyzed by western blot. The co-localization of mitotracker with LC3-II was analyzed by immunofluorescence assays. The flow cytometer was used to evaluate ROS levels.
Results:
All four kinds of siderophores (10 μM) secreted by K. pneumoniae increased the expression of LC3 II and reduced the expression of mitochondrial membrane protein, TOMM20, and TIMM23. Immunofluorescence assays revealed that the treatment of enterobactin significantly increased the co-localization of mitotracker with LC3-II. All four kinds of siderophores increased the ROS level in platelets. Mitophagy of platelets was activated through several pathways, including PINK1/Parkin- and BNIP3-dependent pathways. We also proved that siderophores increased the expression of caspase3 in platelets, and the expression of caspase3 significantly decreased after the pathways of mitophagy were blocked.
Conclusions:
K. pneumoniae siderophores lead to mitophagy in platelets, and mitophagy further induces apoptosis, which may be a potential treatment of thrombocytopenia in infections.
Insights
Klebsiella pneumoniae siderophores trigger mitophagy in platelets, leading to apoptosis. This process may offer a potential therapeutic strategy for treating thrombocytopenia associated with infections.
Area of Science:
- Platelet biology and pathobiology
- Microbial pathogenesis and host-pathogen interactions
- Cellular signaling and programmed cell death
Background:
- Siderophores from *K. pneumoniae* are virulence factors that chelate iron.
- Iron chelation can induce mitochondrial dysfunction, reactive oxygen species (ROS), mitophagy, and apoptosis.
- The specific effects of siderophores on platelets remain largely unexplored.
Purpose of the Study:
- To investigate the impact of *K. pneumoniae* siderophores on platelet mitophagy and apoptosis.
- To elucidate the molecular mechanisms underlying siderophore-induced platelet responses.
Main Methods:
- *In vitro* treatment of human platelets with various siderophores.
- Western blot analysis of mitophagy and apoptosis-related proteins (TOMM20, TIMM23, LC3, p62, PINK1/Parkin, BNIP3, caspase3).
- Immunofluorescence assays for mitotracker and LC3-II co-localization.
- Flow cytometry to assess reactive oxygen species (ROS) levels.
Main Results:
- Siderophores increased LC3-II expression and decreased mitochondrial proteins (TOMM20, TIMM23).
- Enterobactin treatment enhanced mitotracker and LC3-II co-localization, indicating mitophagy.
- All tested siderophores elevated ROS levels and activated mitophagy via PINK1/Parkin and BNIP3 pathways.
- Siderophore treatment increased caspase3 expression, which was reduced upon mitophagy pathway inhibition.
Conclusions:
- *K. pneumoniae* siderophores induce mitophagy in platelets.
- Platelet mitophagy subsequently triggers apoptosis.
- This siderophore-induced platelet apoptosis presents a potential therapeutic target for infection-related thrombocytopenia.
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