期刊
BIOCHEMISTRY AND BIOPHYSICS REPORTS
卷 29, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbrep.2021.101192
关键词
Apoptosis; Cathelicidin; Innate immunity; Mitochondria; Mitochondria model membranes
资金
- Alfred Foundation
- Gyllenstiernska Krapperups Foundation
- Heart Lung Foundation [20200222]
- Swedish Research Council [2020-00908]
- Swedish Research Council [2020-00908] Funding Source: Swedish Research Council
- Formas [2020-00908] Funding Source: Formas
LL-37 is rapidly internalized by MG63 cells and accumulates in mitochondria. It triggers the release of pro-apoptotic AIF and directly affects mitochondrial membrane structural properties.
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 mu M) 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 mu M) 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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