Stem cells are especially sensitive to oxygen radicals and antioxidants, according to new research from the University of Helsinki. The research, led by Riikka Martikainen was published in Cell Reports.
From the group of Anu Wartiovaara in the Molecular Neurology Research Program of University of Helsinki, the work showed that a small increase in oxygen radicals did not directly lead to cellular damage but disrupted intracellular signaling in stem cells and lead to decrease in their stemness properties.
Treatment with antioxidants was able to improve the stemness properties in these cells. Surprisingly, however, the researchers found that an antioxidant targeted to mitochondria showed dose-dependent toxic effects, particularly on neural stem cells.
Mitochondria are cellular power plants that use oxygen to produce energy. As a by-product they produce reactive oxygen.
Excessive oxygen radicals may cause damage to cells but they are needed in small quantities as important cellular signaling molecules. One of their main functions is to control function of stem cells.
Antioxidants are widely used to block the damage caused by reactive oxygen. To enhance their effect some new antioxidants are targeted to accumulate into mitochondria.
The use of antioxidants as dietary supplements is widespread, but little is known of their effects on stem cells.
This new research shows that large doses of antioxidants may be harmful to neural stem cells. Additional research on stem cells should be done to assess safety of mitochondria targeted antioxidants.
Riikka H. Hämäläinen, Kati J. Ahlqvist, Pekka Ellonen, Maija Lepistö, Angela Logan, Timo Otonkoski, Michael P. Murphy, Anu Suomalainen. mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling. Cell Reports, 2015; DOI: 10.1016/j.celrep.2015.05.009
“mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS)/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs) and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associated with an increase in mitochondrial H2O2, reduced PSC reprogramming efficiency, and self-renewal.
Mitochondria-targeted ubiquinone, MitoQ, and N-acetyl-L-cysteine efficiently rescued these defects, indicating that both reprogramming efficiency and stemness are modified by mitochondrial ROS. The redox sensitivity, however, rendered PSCs and especially neural stem cells sensitive to MitoQ toxicity. Our results imply that stem cell compartment warrants special attention when the safety of new antioxidants is assessed and point to an essential role for mitochondrial redox signaling in maintaining normal stem cell function.”
Illustration: Medical University of Vienna