Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences.
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.
Berneburg
Mark
M
Molecular Oncology and Aging, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.
Gremmel
Tobias
T
Kürten
Viola
V
Schroeder
Peter
P
Hertel
Ines
I
von Mikecz
Anna
A
Wild
Susanne
S
Chen
Min
M
Declercq
Lieve
L
Matsui
Mary
M
Ruzicka
Thomas
T
Krutmann
Jean
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003401:Creatine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics*; D016296:Mutagenesis / Q000187:drug effects* / Q000528:radiation effects; D010101:Oxygen Consumption / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000166:cytology; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D000975:Antioxidants; D002250:Carbon Radioisotopes; D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D020781:Matrix Metalloproteinase 1; D003401:Creatine