Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA

Research output: Contribution to journalArticlepeer-review

Standard

Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA. / Nerlich, Andreas; Mieth, Maren; Letsiou, Eleftheria; Fatykhova, Diana; Zscheppang, Katja; Imai-Matsushima, Aki; Meyer, Thomas F; Paasch, Lisa; Mitchell, Timothy J; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Eggeling, Stephan; Schimek, Maria; Witzenrath, Martin; Suttorp, Norbert; Hippenstiel, Stefan; Hocke, Andreas C.

In: Scientific Reports, Vol. 8, No. 1, 182, 09.01.2018.

Research output: Contribution to journalArticlepeer-review

Harvard

Nerlich, A, Mieth, M, Letsiou, E, Fatykhova, D, Zscheppang, K, Imai-Matsushima, A, Meyer, TF, Paasch, L, Mitchell, TJ, Tönnies, M, Bauer, TT, Schneider, P, Neudecker, J, Rückert, JC, Eggeling, S, Schimek, M, Witzenrath, M, Suttorp, N, Hippenstiel, S & Hocke, AC 2018, 'Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA', Scientific Reports, vol. 8, no. 1, 182. https://doi.org/10.1038/s41598-017-18468-7

APA

Nerlich, A., Mieth, M., Letsiou, E., Fatykhova, D., Zscheppang, K., Imai-Matsushima, A., Meyer, T. F., Paasch, L., Mitchell, T. J., Tönnies, M., Bauer, T. T., Schneider, P., Neudecker, J., Rückert, J. C., Eggeling, S., Schimek, M., Witzenrath, M., Suttorp, N., Hippenstiel, S., & Hocke, A. C. (2018). Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA. Scientific Reports, 8(1), [182]. https://doi.org/10.1038/s41598-017-18468-7

Vancouver

Nerlich A, Mieth M, Letsiou E, Fatykhova D, Zscheppang K, Imai-Matsushima A et al. Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA. Scientific Reports. 2018 Jan 9;8(1). 182. https://doi.org/10.1038/s41598-017-18468-7

Author

Nerlich, Andreas ; Mieth, Maren ; Letsiou, Eleftheria ; Fatykhova, Diana ; Zscheppang, Katja ; Imai-Matsushima, Aki ; Meyer, Thomas F ; Paasch, Lisa ; Mitchell, Timothy J ; Tönnies, Mario ; Bauer, Torsten T ; Schneider, Paul ; Neudecker, Jens ; Rückert, Jens C ; Eggeling, Stephan ; Schimek, Maria ; Witzenrath, Martin ; Suttorp, Norbert ; Hippenstiel, Stefan ; Hocke, Andreas C. / Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA. In: Scientific Reports. 2018 ; Vol. 8, No. 1.

Bibtex

@article{5f7f770db44c471db569c6a01ca6d1ec,
title = "Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA",
abstract = "Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment.",
keywords = "Cell death and immune response, Cellular microbiology, Infection",
author = "Andreas Nerlich and Maren Mieth and Eleftheria Letsiou and Diana Fatykhova and Katja Zscheppang and Aki Imai-Matsushima and Meyer, {Thomas F} and Lisa Paasch and Mitchell, {Timothy J} and Mario T{\"o}nnies and Bauer, {Torsten T} and Paul Schneider and Jens Neudecker and R{\"u}ckert, {Jens C} and Stephan Eggeling and Maria Schimek and Martin Witzenrath and Norbert Suttorp and Stefan Hippenstiel and Hocke, {Andreas C}",
year = "2018",
month = jan,
day = "9",
doi = "10.1038/s41598-017-18468-7",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA

AU - Nerlich, Andreas

AU - Mieth, Maren

AU - Letsiou, Eleftheria

AU - Fatykhova, Diana

AU - Zscheppang, Katja

AU - Imai-Matsushima, Aki

AU - Meyer, Thomas F

AU - Paasch, Lisa

AU - Mitchell, Timothy J

AU - Tönnies, Mario

AU - Bauer, Torsten T

AU - Schneider, Paul

AU - Neudecker, Jens

AU - Rückert, Jens C

AU - Eggeling, Stephan

AU - Schimek, Maria

AU - Witzenrath, Martin

AU - Suttorp, Norbert

AU - Hippenstiel, Stefan

AU - Hocke, Andreas C

PY - 2018/1/9

Y1 - 2018/1/9

N2 - Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment.

AB - Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment.

KW - Cell death and immune response

KW - Cellular microbiology

KW - Infection

U2 - 10.1038/s41598-017-18468-7

DO - 10.1038/s41598-017-18468-7

M3 - Article

C2 - 29317705

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 182

ER -