Mitochondria and AMP-activated protein kinase-dependent mechanism of efferocytosis

Shaoning Jiang1, Dae Won Park2, William S Stigler1

  • 1From the Department of Medicine.

Insights

AMP-activated kinase (AMPK) activation in macrophages enhances the clearance of apoptotic cells, crucial for resolving inflammation and restoring tissue homeostasis. This mitochondrial AMPK pathway aids in tracking and engulfing dying cells.

Area of Science:

  • Cell Biology
  • Immunology
  • Mitochondrial Biology

Background:

  • Defective clearance of apoptotic cells contributes to chronic inflammatory diseases.
  • Understanding the molecular mechanisms of efferocytosis is critical for therapeutic interventions.

Purpose of the Study:

  • To investigate the role of AMP-activated kinase (AMPK) in the clearance of apoptotic cells.
  • To elucidate the signaling pathways involved in AMPK activation during efferocytosis.

Main Methods:

  • Macrophages were exposed to apoptotic cells and lysophosphatidylcholine.
  • AMPK activation was assessed by measuring mitochondrial function, calcium mobilization, and reactive oxygen species.
  • Apoptotic cell uptake was quantified in vitro and in vivo in mouse models.

Main Results:

  • Apoptotic cells and lysophosphatidylcholine rapidly activated AMPK in macrophages.
  • AMPK activation was dependent on mitochondrial dysfunction, Ca(2+) flux, and mitochondrial ROS.
  • Activated AMPK enhanced microtubule synthesis, chemokinesis, and apoptotic cell engulfment.
  • Inhibition of AMPK impaired apoptotic cell clearance in vitro and in vivo.

Conclusions:

  • The mitochondrial AMPK axis acts as a critical sensor and enhancer for apoptotic cell tracking and removal.
  • AMPK-mediated efferocytosis is essential for resolving inflammation and maintaining tissue homeostasis.

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