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Emma Sparr. Portrait.

Emma Sparr

Professor

Emma Sparr. Portrait.

The antimicrobial peptide LL-37 triggers release of apoptosis-inducing factor and shows direct effects on mitochondria

Author

  • Elisabeth Bankell
  • Xiaoyan Liu
  • Martin Lundqvist
  • Daniel Svensson
  • Karl Swärd
  • Emma Sparr
  • Bengt Olof Nilsson

Summary, in English

The human antimicrobial peptide LL-37 permeabilizes the plasma membrane of host cells, but LL-37-induced direct effects on mitochondrial membrane permeability and function has not been reported. Here, we demonstrate that LL-37 is rapidly (within 20 min) internalized by human osteoblast-like MG63 cells, and that the peptide co-localizes with MitoTracker arguing for accumulation in mitochondria. Subcellular fractionation and Western blot disclose that stimulation with LL-37 (8 μM) for 2 h triggers release of the mitochondrial protein apoptosis-inducing factor (AIF) to the cytosol, whereas LL-37 causes no release of cytochrome C oxidase subunit IV of the inner mitochondrial membrane, suggesting that LL-37 affects mitochondrial membrane permeability in a specific manner. Next, we investigated release of AIF and cytochrome C from isolated mitochondria by measuring immunoreactivity by dot blot. The media of mitochondria treated with LL-37 (8 μM) for 2 h contained 50% more AIF and three times more cytochrome C than that of control mitochondria, showing that LL-37 promotes release of both AIF and cytochrome C. Moreover, in vesicles reflecting mitochondrial membrane lipid composition, LL-37 stimulates membrane permeabilization and release of tracer molecules. We conclude that LL-37 is rapidly internalized by MG63 cells and accumulates in mitochondria, and that the peptide triggers release of pro-apoptotic AIF and directly affects mitochondrial membrane structural properties.

Department/s

  • Vascular Physiology
  • Physical Chemistry
  • Biochemistry and Structural Biology
  • NanoLund: Centre for Nanoscience
  • Cellular Biomechanics
  • MultiPark: Multidisciplinary research on neurodegenerative diseases

Publishing year

2022-03

Language

English

Publication/Series

Biochemistry and Biophysics Reports

Volume

29

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology

Keywords

  • Apoptosis
  • Cathelicidin
  • Innate immunity
  • Mitochondria
  • Mitochondria model membranes

Status

Published

Research group

  • Vascular Physiology
  • Cellular Biomechanics

ISBN/ISSN/Other

  • ISSN: 2405-5808