Universität zu Köln

Weiland, Daniela, Brachvogel, Bent, Hornig-Do, Hue-Tran, Neuhaus, Johannes F. G., Holzer, Tatjana, Tobin, Desmond J., Niessen, Carien M., Wiesner, Rudolf J. and Baris, Olivier R. (2018). Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation. J. Invest. Dermatol., 138 (1). S. 132 - 141. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Accumulation of large-scale mitochondrial DNA (mtDNA) deletions and chronic, subclinical inflammation are concomitant during skin aging, thus raising the question of a causal link. To approach this, we generated mice expressing a mutant mitochondrial helicase (K320E-TWINKLE) in the epidermis to accelerate the accumulation of mtDNA deletions in this skin compartment. Mice displayed low amounts of large-scale deletions and a dramatic depletion of mtDNA in the epidermis and showed macroscopic signs of severe skin inflammation. The mtDNA alterations led to an imbalanced stoichiometry of mitochondrial respiratory chain complexes, inducing a unique combination of cytokine expression, causing a severe inflammatory phenotype, with massive immune cell infiltrates already before birth. Altogether, these data unraveled a previously unknown link between an imbalanced stoichiometry of the mitochondrial respiratory chain complexes and skin inflammation and suggest that severe respiratory chain dysfunction, as observed in few cells leading to a mosaic in aged tissues, might be involved in the development of chronic subclinical inflammation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weiland, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED Hornig-Do, Hue-Tran UNSPECIFIED UNSPECIFIED UNSPECIFIED Neuhaus, Johannes F. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holzer, Tatjana UNSPECIFIED UNSPECIFIED UNSPECIFIED Tobin, Desmond J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204893
DOI:	10.1016/j.jid.2017.08.019
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	138
Number:	1
Page Range:	S. 132 - 141
Date:	2018
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA DELETIONS; NLRP3 INFLAMMASOME; MUTATIONS; DEGENERATION; STABILITY; EXPOSURE; MEDIATOR; TWINKLE; RATHER; MARKER Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20489