Siderophores induce mitophagy-dependent apoptosis in platelets

Wenyuan Wang1, Yufeng Lu1, Yulin Wang2

  • 1Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China.

Abstract

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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