Original Article
Subject Categories: Cell Biology

Journal of Investigative Dermatology (2005) 125, 213–220; doi:10.1111/j.0022-202X.2005.23806.x

Creatine Supplementation Normalizes Mutagenesis of Mitochondrial DNA as Well as Functional Consequences
Mark Berneburg*, Tobias Gremmel†, Viola Kürten†, Peter Schroeder†, Ines Hertel†, Anna von Mikecz†, Susanne Wild†, Min Chen†, Lieve Declercq‡, Mary Matsui§, Thomas Ruzicka¶ and Jean Krutmann†

*Molecular Oncology and Aging, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
†Institut für Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universität Düsseldorf gGmbH, Düsseldorf, Germany
‡Biological Research Department Europe, Estée Lauder BCC, Oevel, Belgium
§Biological Research Department Estée Lauder Companies, Melville, New York, USA
¶Department of Dermatology, Heinrich-Heine-University, Duesseldorf, Germany
Correspondence: Jean Krutmann, Institut für Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universität Düsseldorf gGmbH, Auf'm Hennekamp 50, D-40225 Düsseldorf, Germany. Email: krutmann@rz.uni-duesseldorf.de

Received 20 September 2004; Revised 16 February 2005; Accepted 3 March 2005.

Top of pageAbstract
Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal aging, premature aging of the skin (photoaging), and tumors. We and others could demonstrate that mtDNA mutations can be induced in skin cells in vitro and in normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A-irradiation. These mutations are mediated by singlet oxygen and persist in human skin as long-term biomarkers of UV exposure. Although mtDNA exclusively encodes for the respiratory chain, involvement of the energy metabolism in mtDNA mutagenesis and a protective role of the energy precursor creatine have thus far not been shown. We assessed the amount of a marker mutation of mtDNA, the so-called common deletion, by real-time PCR. Induction of the common deletion was paralleled by a measurable decrease of oxygen consumption, mitochondrial membrane potential, and ATP content, as well as an increase of matrix metalloproteinase-1. Mitochondrial mutagenesis as well as functional consequences could be normalized by increasing intracellular creatine levels. These data indicate that increase of the energy precursor creatine protects from functionally relevant, aging-associated mutations of mitochondrial DNA.