The antimicrobial peptide LL-37 triggers release of apoptosis-inducing factor and shows direct effects on mitochondria
(2022) In Biochemistry and Biophysics Reports 29.- Abstract
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... (More)
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.
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- author
- Bankell, Elisabeth LU ; Liu, Xiaoyan LU ; Lundqvist, Martin LU ; Svensson, Daniel LU ; Swärd, Karl LU ; Sparr, Emma LU and Nilsson, Bengt Olof LU
- organization
- publishing date
- 2022-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Apoptosis, Cathelicidin, Innate immunity, Mitochondria, Mitochondria model membranes
- in
- Biochemistry and Biophysics Reports
- volume
- 29
- article number
- 101192
- publisher
- Elsevier
- external identifiers
-
- pmid:34988298
- scopus:85121378636
- ISSN
- 2405-5808
- DOI
- 10.1016/j.bbrep.2021.101192
- language
- English
- LU publication?
- yes
- id
- e77538b3-ff03-4fa4-a58b-2411139cbbe8
- date added to LUP
- 2022-01-25 14:25:50
- date last changed
- 2024-10-06 12:18:35
@article{e77538b3-ff03-4fa4-a58b-2411139cbbe8, abstract = {{<p>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.</p>}}, author = {{Bankell, Elisabeth and Liu, Xiaoyan and Lundqvist, Martin and Svensson, Daniel and Swärd, Karl and Sparr, Emma and Nilsson, Bengt Olof}}, issn = {{2405-5808}}, keywords = {{Apoptosis; Cathelicidin; Innate immunity; Mitochondria; Mitochondria model membranes}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{Biochemistry and Biophysics Reports}}, title = {{The antimicrobial peptide LL-37 triggers release of apoptosis-inducing factor and shows direct effects on mitochondria}}, url = {{http://dx.doi.org/10.1016/j.bbrep.2021.101192}}, doi = {{10.1016/j.bbrep.2021.101192}}, volume = {{29}}, year = {{2022}}, }